N-(diethoxyphosphorylmethyl)-1-phenylmethanimine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzylamine in absolute alcohol is added a molar equivalent of 37% aqueous formaldehyde and the reaction mixture is allowed to stir at room temperature for 2 hours. The 1,3,5-tribenzyl-sym-hexahydrotriazine found in the reaction is recovered by extraction with petroleum ether which, after evaporation, yields a product melting at 48°-50°C. The latter product is heated with about 3 molar equivalents of diethyl phosphite at 100°C. for 6 hours, and the resulting reaction product is chromatographed on silica gel using 3% methanol in methylene chloride as the eluting solvent. Evaporation of the solvent affords diethyl N-benzylaminomethylphosphonate as a pale yellow mobile liquid. Hydrogenation of this product is absolute alcohol containing a small amount of HCl in the presence of palladium on carbon catalyst affords diethyl aminomethylphosphonate hydrochloride which is recovered by evaporating the filtered hydrogenation mixture. Reaction of this product in chloroform with ammonia and evaporation of the resulting filtered solution yields diethyl aminomethylphosphonate. Benzaldehyde is added to this product in an ice bath to produce diethyl N-benzylidene-aminomethylphosphonate which is recovered by diluting the reaction mixture with absolute alcohol and evaporating the filtered solution. The product is further purified by solution in dry benzene and evaporation of the solvent to afford the product as a pale yellow oil. To a solution of the diethyl N-benzylidene-aminomethylphosphonate in dry tetrahydrofuran is then added phenyllithium solution followed by the slow addition of p-methoxybenzyl chloroformate. After about 20 minutes, the solvent is removed under reduced pressure and the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer. Evaporation of the ethyl ether affords p-methoxybenzyl N-benzylidene-α-amino-diethylphosphonoacetate which is purified by chromatography over silica gel using 1:3 ethyl acetateethyl ether as the eluting solvent. The product so obtained is reacted with p-toluenesulfonic acid in ethyl ether solution and cyclohexane is added to the reaction mixture. The solvent layer is decanted and the resulting oily layer is again washed with 2:1 ethyl ether-cyclohexane. Solution of the oily residue in aqueous dipotassium phosphate to pH about 7 and extraction of the solution with methylene chloride affords a solvent solution of the product which is evaporated to produce p-methoxybenzyl α-amino-diethylphosphonoacetate. Reaction of this product with ethyl thioformate in the presence of liquid hydrogen sulfide at low temperatures produces crude p-methoxybenzyl α-thioformamido-diethylphosphonoacetate. The latter product is purified over silica gel using ethyl acetate to elute the product. is recovered by diluting the reaction mixture with absolute alcohol evaporating the filtered solution The product is further purified by solution in dry benzene evaporation of the solvent to afford the product as a pale yellow oil the solvent is removed under reduced pressure the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer Evaporation of the ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzylamine in absolute alcohol is added a molar equivalent of 37% aqueous formaldehyde and the reaction mixture is allowed to stir at room temperature for 2 hours. The 1,3,5-tribenzyl-sym-hexahydrotriazine found in the reaction is recovered by extraction with petroleum ether which, after evaporation, yields a product melting at 48°-50°C. The latter product is heated with about 3 molar equivalents of diethyl phosphite at 100°C. for 6 hours, and the resulting reaction product is chromatographed on silica gel using 3% methanol in methylene chloride as the eluting solvent. Evaporation of the solvent affords diethyl N-benzylaminomethylphosphonate as a pale yellow mobile liquid. Hydrogenation of this product is absolute alcohol containing a small amount of HCl in the presence of palladium on carbon catalyst affords diethyl aminomethylphosphonate hydrochloride which is recovered by evaporating the filtered hydrogenation mixture. Reaction of this product in chloroform with ammonia and evaporation of the resulting filtered solution yields diethyl aminomethylphosphonate. Benzaldehyde is added to this product in an ice bath to produce diethyl N-benzylidene-aminomethylphosphonate which is recovered by diluting the reaction mixture with absolute alcohol and evaporating the filtered solution. The product is further purified by solution in dry benzene and evaporation of the solvent to afford the product as a pale yellow oil. To a solution of the diethyl N-benzylidene-aminomethylphosphonate in dry tetrahydrofuran is then added phenyllithium solution followed by the slow addition of p-methoxybenzyl chloroformate. After about 20 minutes, the solvent is removed under reduced pressure and the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer. Evaporation of the ethyl ether affords p-methoxybenzyl N-benzylidene-α-amino-diethylphosphonoacetate which is purified by chromatography over silica gel using 1:3 ethyl acetateethyl ether as the eluting solvent. The product so obtained is reacted with p-toluenesulfonic acid in ethyl ether solution and cyclohexane is added to the reaction mixture. The solvent layer is decanted and the resulting oily layer is again washed with 2:1 ethyl ether-cyclohexane. Solution of the oily residue in aqueous dipotassium phosphate to pH about 7 and extraction of the solution with methylene chloride affords a solvent solution of the product which is evaporated to produce p-methoxybenzyl α-amino-diethylphosphonoacetate. Reaction of this product with ethyl thioformate in the presence of liquid hydrogen sulfide at low temperatures produces crude p-methoxybenzyl α-thioformamido-diethylphosphonoacetate. The latter product is purified over silica gel using ethyl acetate to elute the product. is recovered by diluting the reaction mixture with absolute alcohol evaporating the filtered solution The product is further purified by solution in dry benzene evaporation of the solvent to afford the product as a pale yellow oil the solvent is removed under reduced pressure the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer Evaporation of the ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzylamine in absolute alcohol is added a molar equivalent of 37% aqueous formaldehyde and the reaction mixture is allowed to stir at room temperature for 2 hours. The 1,3,5-tribenzyl-sym-hexahydrotriazine found in the reaction is recovered by extraction with petroleum ether which, after evaporation, yields a product melting at 48°-50°C. The latter product is heated with about 3 molar equivalents of diethyl phosphite at 100°C. for 6 hours, and the resulting reaction product is chromatographed on silica gel using 3% methanol in methylene chloride as the eluting solvent. Evaporation of the solvent affords diethyl N-benzylaminomethylphosphonate as a pale yellow mobile liquid. Hydrogenation of this product is absolute alcohol containing a small amount of HCl in the presence of palladium on carbon catalyst affords diethyl aminomethylphosphonate hydrochloride which is recovered by evaporating the filtered hydrogenation mixture. Reaction of this product in chloroform with ammonia and evaporation of the resulting filtered solution yields diethyl aminomethylphosphonate. Benzaldehyde is added to this product in an ice bath to produce diethyl N-benzylidene-aminomethylphosphonate which is recovered by diluting the reaction mixture with absolute alcohol and evaporating the filtered solution. The product is further purified by solution in dry benzene and evaporation of the solvent to afford the product as a pale yellow oil. To a solution of the diethyl N-benzylidene-aminomethylphosphonate in dry tetrahydrofuran is then added phenyllithium solution followed by the slow addition of p-methoxybenzyl chloroformate. After about 20 minutes, the solvent is removed under reduced pressure and the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer. Evaporation of the ethyl ether affords p-methoxybenzyl N-benzylidene-α-amino-diethylphosphonoacetate which is purified by chromatography over silica gel using 1:3 ethyl acetateethyl ether as the eluting solvent. The product so obtained is reacted with p-toluenesulfonic acid in ethyl ether solution and cyclohexane is added to the reaction mixture. The solvent layer is decanted and the resulting oily layer is again washed with 2:1 ethyl ether-cyclohexane. Solution of the oily residue in aqueous dipotassium phosphate to pH about 7 and extraction of the solution with methylene chloride affords a solvent solution of the product which is evaporated to produce p-methoxybenzyl α-amino-diethylphosphonoacetate. Reaction of this product with ethyl thioformate in the presence of liquid hydrogen sulfide at low temperatures produces crude p-methoxybenzyl α-thioformamido-diethylphosphonoacetate. The latter product is purified over silica gel using ethyl acetate to elute the product. is recovered by diluting the reaction mixture with absolute alcohol evaporating the filtered solution The product is further purified by solution in dry benzene evaporation of the solvent to afford the product as a pale yellow oil the solvent is removed under reduced pressure the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer Evaporation of the ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzylamine in absolute alcohol is added a molar equivalent of 37% aqueous formaldehyde and the reaction mixture is allowed to stir at room temperature for 2 hours. The 1,3,5-tribenzyl-sym-hexahydrotriazine found in the reaction is recovered by extraction with petroleum ether which, after evaporation, yields a product melting at 48°-50°C. The latter product is heated with about 3 molar equivalents of diethyl phosphite at 100°C. for 6 hours, and the resulting reaction product is chromatographed on silica gel using 3% methanol in methylene chloride as the eluting solvent. Evaporation of the solvent affords diethyl N-benzylaminomethylphosphonate as a pale yellow mobile liquid. Hydrogenation of this product is absolute alcohol containing a small amount of HCl in the presence of palladium on carbon catalyst affords diethyl aminomethylphosphonate hydrochloride which is recovered by evaporating the filtered hydrogenation mixture. Reaction of this product in chloroform with ammonia and evaporation of the resulting filtered solution yields diethyl aminomethylphosphonate. Benzaldehyde is added to this product in an ice bath to produce diethyl N-benzylidene-aminomethylphosphonate which is recovered by diluting the reaction mixture with absolute alcohol and evaporating the filtered solution. The product is further purified by solution in dry benzene and evaporation of the solvent to afford the product as a pale yellow oil. To a solution of the diethyl N-benzylidene-aminomethylphosphonate in dry tetrahydrofuran is then added phenyllithium solution followed by the slow addition of p-methoxybenzyl chloroformate. After about 20 minutes, the solvent is removed under reduced pressure and the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer. Evaporation of the ethyl ether affords p-methoxybenzyl N-benzylidene-α-amino-diethylphosphonoacetate which is purified by chromatography over silica gel using 1:3 ethyl acetateethyl ether as the eluting solvent. The product so obtained is reacted with p-toluenesulfonic acid in ethyl ether solution and cyclohexane is added to the reaction mixture. The solvent layer is decanted and the resulting oily layer is again washed with 2:1 ethyl ether-cyclohexane. Solution of the oily residue in aqueous dipotassium phosphate to pH about 7 and extraction of the solution with methylene chloride affords a solvent solution of the product which is evaporated to produce p-methoxybenzyl α-amino-diethylphosphonoacetate. Reaction of this product with ethyl thioformate in the presence of liquid hydrogen sulfide at low temperatures produces crude p-methoxybenzyl α-thioformamido-diethylphosphonoacetate. The latter product is purified over silica gel using ethyl acetate to elute the product. is recovered by diluting the reaction mixture with absolute alcohol evaporating the filtered solution The product is further purified by solution in dry benzene evaporation of the solvent to afford the product as a pale yellow oil the solvent is removed under reduced pressure the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer Evaporation of the ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzylamine in absolute alcohol is added a molar equivalent of 37% aqueous formaldehyde and the reaction mixture is allowed to stir at room temperature for 2 hours. The 1,3,5-tribenzyl-sym-hexahydrotriazine found in the reaction is recovered by extraction with petroleum ether which, after evaporation, yields a product melting at 48°-50° C. The latter product is heated with about 3 molar equivalents of diethyl phosphite at 100° C. for 6 hours, and the resulting reaction product is chromatographed on silica gel using 3% methanol in methylene chloride as the eluting solvent. Evaporation of the solvent affords diethyl N-benzyl-aminomethylphosphonate as a pale yellow mobile liquid. Hydrogenation of this product in absolute alcohol containing a small amount of HCl in the presence of palladium on carbon catalyst affords diethyl aminomethylphosphonate hydrochloride which is recovered by evaporating the filtered hydrogenation mixture. Reaction of this product in chloroform with ammonia and evaporation of the resulting filtered solution yields diethyl aminomethylphosphonate. Benzaldehyde is added to this product in an ice bath to produce diethyl N-benzylidene-aminomethylphosphonate which is recovered by diluting the reaction mixture with absolute alcohol and evaporating the filtered solution. The product is further purified by solution in dry benzene and evaporation of the solvent to afford the product as a pale yellow oil. To a solution of the diethyl N-benzylidene-aminomethylphosphonate in dry tetrahydrofuran is then added phenyllithium solution followed by the slow addition of p-methoxybenzyl chloroformate. After about 20 minutes, the solvent is removed under reduced pressure and the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer. Evaporation of the ethyl ether affords p-methoxybenzyl N-benzylidene-α-amino-diethylphosphonoacetate which is purified by chromatography over silica gel using 1:3 ethyl acetate-ethyl ether as the eluting solvent. The product so obtained is reacted with p-toluenesulfonic acid in ethyl ether solution and cyclohexane is added to the reaction mixture. The solvent layer is decanted and the resulting oily layer is again washed with 2:1 ethyl ether-cyclohexane. Solution of the oily residue in aqueous dipotassium phosphate to pH about 7 and extraction of the solution with methylene chloride affords a solvent solution of the product which is evaporated to produce p-methoxybenzyl α-amino-diethylphosphonoacetate. Reaction of this product with ethyl thioformate in the presence of liquid hydrogen sulfide at low temperatures produces crude p-methoxybenzyl α-thioformamido-diethylphosphonoacetate. The latter product is purified over silica gel using ethyl acetate to elute the product. is recovered by diluting the reaction mixture with absolute alcohol evaporating the filtered solution The product is further purified by solution in dry benzene evaporation of the solvent to afford the product as a pale yellow oil the solvent is removed under reduced pressure the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer Evaporation of the ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzylamine in absolute alcohol is added a molar equivalent of 37% aqueous formaldehyde and the reaction mixture is allowed to stir at room temperature for 2 hours. The 1,3,5-tribenzyl-sym-hexahydrotriazine found in the reaction is recovered by extraction with petroleum ether which, after evaporation, yields a product melting at 48°-50° C. The latter product is heated with about 3 molar equivalents of diethyl phosphite at 100° C. for 6 hours, and the resulting reaction product is chromatographed on silica gel using 3% methanol in methylene chloride as the eluting solvent. Evaporation of the solvent affords diethyl N-benzyl-aminomethylphosphonate as a pale yellow mobile liquid. Hydrogenation of this product in absolute alcohol containing a small amount of HCl in the presence of palladium on carbon catalyst affords diethyl aminomethylphosphonate hydrochloride which is recovered by evaporating the filtered hydrogenation mixture. Reaction of this product in chloroform with ammonia and evaporation of the resulting filtered solution yields diethyl aminomethylphosphonate. Benzaldehyde is added to this product in an ice bath to produce diethyl N-benzylidene-aminomethylphosphonate which is recovered by diluting the reaction mixture with absolute alcohol and evaporating the filtered solution. The product is further purified by solution in dry benzene and evaporation of the solvent to afford the product as a pale yellow oil. To a solution of the diethyl N-benzylidene-aminomethylphosphonate in dry tetrahydrofuran is then added phenyllithium solution followed by the slow addition of p-methoxybenzyl chloroformate. After about 20 minutes, the solvent is removed under reduced pressure and the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer. Evaporation of the ethyl ether affords p-methoxybenzyl N-benzylidene-α-amino-diethylphosphonoacetate which is purified by chromatography over silica gel using 1:3 ethyl acetate-ethyl ether as the eluting solvent. The product so obtained is reacted with p-toluenesulfonic acid in ethyl ether solution and cyclohexane is added to the reaction mixture. The solvent layer is decanted and the resulting oily layer is again washed with 2:1 ethyl ether-cyclohexane. Solution of the oily residue in aqueous dipotassium phosphate to pH about 7 and extraction of the solution with methylene chloride affords a solvent solution of the product which is evaporated to produce p-methoxybenzyl α-amino-diethylphosphonoacetate. Reaction of this product with ethyl thioformate in the presence of liquid hydrogen sulfide at low temperatures produces crude p-methoxybenzyl α-thioformamido-diethylphosphonoacetate. The latter product is purified over silica gel using ethyl acetate to elute the product. is recovered by diluting the reaction mixture with absolute alcohol evaporating the filtered solution The product is further purified by solution in dry benzene evaporation of the solvent to afford the product as a pale yellow oil the solvent is removed under reduced pressure the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer Evaporation of the ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of diethyl N-benzylidene-aminomethylphosphonate (12.738 g., 50 mmole) in dry tetrahydrofuran (250 ml.) is stirred in a dry ice-acetone bath and under a nitrogen atmosphere. Phenyllithium (25 ml. of a 2.0 M solution in 7:3 benzene-ethyl ether) is added via syringe. The resulting burgundy solution is stirred for 30 minutes at -78°C., then treated dropwise over 45 minutes with a solution of 2,2,2-trichloroethyoxycarbonyl chloride (5.30 g., 25 mmole) in dry tetrahydrofuran (50 ml.). After stirring the mixture for an additional 2 hours at -78°C., the dry ice bath is replaced by an ice water bath and stirring is continued for 1 hour. Evaporation of the solvent in vacuo leaves a yellow foam which is partitioned between ethyl ether (250 ml.) and aqueous phosphate (50 ml. of 1M pH 3 phosphate + 50 ml. water). The aqueous portion is separated and extracted with ethyl ether (2 × 50 ml.). The combined ethereal solution is washed with saturated brine (100 ml.), dried over magnesium sulfate, and evaporated in vacuo to yield a cloudy, yellow oil (17.1 g.). The crude product is purified by chromatography on silica gel (430 g., packed under ethyl ether). Elution with ethyl ether affords trichloroethyl N-benzylidene-α-amino-diethylphosphonoacetate (7.058 g.) as a yellow oil. After stirring the mixture for an additional 2 hours at -78°C. stirring is continued for 1 hour Evaporation of the solvent in vacuo leaves a yellow foam which is partitioned between ethyl ether (250 ml.) and aqueous phosphate (50 ml. of 1M pH 3 phosphate + 50 ml. water) The aqueous portion is separated extracted with ethyl ether (2 × 50 ml.) The combined ethereal solution is washed with saturated brine (100 ml.) dried over magnesium sulfate evaporated in vacuo to yield a cloudy, yellow oil (17.1 g.) The crude product is purified by chromatography on silica gel (430 g., packed under ethyl ether) Elution with ethyl ether

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenyllithium (12.5 ml. of a 2.0M solution in 7:3 benzene-ethyl ether) is added to a dry-ice cooled, stirring solution of diethyl N-benzylidene-aminomethylphosphonate (6.073 g., 23.8 mMol) in dry tetrahydrofuran (130 ml.). After having been stirred for 30 minutes at -78°C. under a N2 atmosphere, the solution is treated dropwise over 25 minutes with a solution of trichloroethyl chloroformate (5.04 g., 23.8 mMol) in dry tetrahydrofuran (25 ml.). The resulting solution is stirred an additional 2 hours at -78°C., then allowed to warm to 3°C. over a period of 30 minutes. Evaporation of the solvent in vacuo yields a yellow foam which is partitioned between ethyl ether (150 ml.) and 0.5M pH3 phosphate buffer (50 ml.). The aqueous phase is separated and extracted with two additional portions of ether (25 ml.). The combined ethereal solution is washed with saturated brine (100 ml.), dried over MgSO4, and evaporated under reduced pressure to give a cloudy, yellow oil. Chromatography of the crude product on silica gel (200 g.) using 9:1 ethyl acetate-acetone as eluting solvent gives trichloroethyl N-benzylidene-α-amino-diethylphosphonoacetate as a pale yellow oil. cooled The resulting solution is stirred an additional 2 hours at -78°C. to warm to 3°C. over a period of 30 minutes Evaporation of the solvent in vacuo yields a yellow foam which is partitioned between ethyl ether (150 ml.) and 0.5M pH3 phosphate buffer (50 ml.) The aqueous phase is separated extracted with two additional portions of ether (25 ml.) The combined ethereal solution is washed with saturated brine (100 ml.) dried over MgSO4 evaporated under reduced pressure to give a cloudy, yellow oil as eluting solvent

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl aminomethylphosphonate (4.03 g., 24.1 mmole) is stirred in an ice bath while benzaldehyde (2.50 ml., 24.5 mMol) is added dropwise over a period of 5 minutes. After having been stirred an additional 15 minutes at 0°C., the mixture is diluted with absolute ethanol (20 ml.) and evaporated in vacuo. The residue is dissolved in dry benzene (20 ml.) and evaporated to give diethyl N-benzylidene-aminomethylphosphonate (6.073 g.) as a pale yellow oil: ir (CCl4) 1639, 1250, 1062, 1037, and 971 cm-1 ; nmr (CDCl3)τ8.68 (t, 6, J=7 Hz, CH3), 5.93 (d of d, 2, J=17.5 Hz and J=1 Hz, CH2), 5.85 (d of q, 4, J=8 Hz and J=7 Hz, CH2CH3), 2.65 (m, 3, ArH), 2.29 (m, 2, ArH), and 1.75 (t of d, 1, J=1 Hz and J=5 Hz, =CH). is added dropwise over a period of 5 minutes evaporated in vacuo The residue is dissolved in dry benzene (20 ml.) evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzylamine in absolute alcohol is added a molar equivalent of 37% aqueous formaldehyde and the reaction mixture is allowed to stir at room temperature for 2 hours. The 1,3,5-tribenzyl-sym-hexahydrotriazine found in the reaction is recovered by extraction with petroleum ether which, after evaporation, yields a product melting at 48°-50° C. The latter product is heated with about 3 molar equivalents of diethyl phosphite at 100° C. for 6 hours, and the resulting reaction product is chromatographed on silica gel using 3% methanol in methylene chloride as the eluting solvent. Evaporation of the solvent affords diethyl N-benzyl-aminomethylphosphonate as a pale yellow mobile liquid. Hydrogenation of this product in absolute alcohol containing a small amount of HCl in the presence of palladium on carbon catalyst affords diethyl aminomethylphosphonate hydrochloride which is recovered by evaporating the filtered hydrogenation mixture. Reaction of this product in chloroform with ammonia and evaporation of the resulting filtered solution yields diethyl aminomethylphosphonate. Benzaldehyde is added to this product in an ice bath to produce diethyl N-benzylidene-aminomethylphosphonate which is recoverd by diluting the reaction mixture with absolute alcohol and evaporating the filtered solution. The product is further purified by solution in dry benzene and evaporation of the solvent to afford the product as a pale yellow oil. To a solution of the diethyl N-benzylidene-aminomethylphosphonate in dry tetrahydrofuran is then added phenyllithium solution followed by the slow addition of p-methoxybenzyl chloroformate. After about 20 minutes, the solvent is removed under reduced pressure and the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer. Evaporation of the ethyl ether affords p-methoxybenzyl N-benzylidene-α-amino-diethylphosphonoacetate which is purified by chromatography over silica gel using 1:3 ethyl acetateethyl ether as the eluting solvent. The product so obtained is reacted with p-toluenesulfonic acid in ethyl ether solution and cyclohexane is added to the reaction mixture. The solvent layer is decanted and the resulting oily layer is again washed with 2:1 ethyl ether-cyclohexane. Solution of the oily residue in aqueous dipotassium phosphate to pH about 7 and extraction of the solution with methylene chloride affords a solvent solution of the product which is evaporated to produce p-methyoxybenzyl α-amino-diethylphosphonoacetate. Reaction of this product with ethyl thioformate in the presence of liquid hydrogen sulfide at low temperatures produces crude p-methoxybenzyl α-thioformamido-diethylphosphonoacetate. The latter product is purified over silica gel using ethyl acetate to elute the product. evaporating the filtered solution The product is further purified by solution in dry benzene evaporation of the solvent to afford the product as a pale yellow oil the solvent is removed under reduced pressure the oily residue is partitioned between ethyl ether and pH 3 phosphate buffer Evaporation of the ethyl ether