1-methoxypropan-2-one

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

Procedure: A solution of 2-methyl-3-butyne-2-ol (25 g, 0.3 mol) in tetrahydrofuran (250 ml) is cooled to −78° C. under a nitrogen atmosphere and to this solution, n-butyl lithium (1.6 molar solution in hexanes, 372 ml, 0.59 mol) is added slowly over 1.5-2.0 hours. The reaction mixture is stirred for 1 hour at −78° C. and a solution of methoxyacetone (38 g, 0.43 mol) in tetrahydrofuran (50 ml) is added. The reaction mixture is stirred at −78° C. for one hour, allowed to come to ambient temperature, and stirred for 2-3 hours. The reaction mixture is cooled to 10° C. and quenched with ice cold water. The mixture is extracted with ethyl acetate (3×250 ml), and the organic phases are combined, washed with water, and dried over anhydrous sodium sulfate. The mixture is filtered, and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give 1-methoxy-2,5-dimethylhex-3-yne-2,5-diol (15 g) as a colourless oil. is added slowly over 1.5-2.0 hours The reaction mixture is stirred at −78° C. for one hour to come to ambient temperature stirred for 2-3 hours The reaction mixture is cooled to 10° C. quenched with ice cold water The mixture is extracted with ethyl acetate (3×250 ml) washed with water dried over anhydrous sodium sulfate The mixture is filtered the filtrate is evaporated under reduced pressure The residue is purified by column chromatography on silica gel

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 500 μL (5.43 mmol) methoxyacetone and 1.05 g (5.43 mmol) N-benzylglycine ethyl ester in 2.0 mL acetic acid was added 780 μl (6.18 mmol) trimethylsilyl cyanide dropwise. The resulting mixture was stirred at 80° C. for 30 min and then poured into ice water. The water was decanted and the oily residue was triturated with DIPE. The precipitate was filtered off and the solvent was washed with saturated aqueous NaHCO3 solution, dried over sodium sulfate, filtered and concentrated in vacuo. The water was decanted the oily residue was triturated with DIPE The precipitate was filtered off the solvent was washed with saturated aqueous NaHCO3 solution dried over sodium sulfate filtered concentrated in vacuo

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

Procedure: A mixture of methyl 2- methyl-5-nitrobenzyl ether (12 g. 0.066 M), methoxyacetone [20 g (used as solvent)], 2-naphthalenesulfonic acid (0.3 g) and 5% Pt/C (0.7 g) is shaken on a Parr hydrogenator maintaining the temperature below 40° with external cooling. The theoretical amount of hydrogen (0.26 M) is consumed and further uptake ceases after 2 hours. maintaining the temperature below 40° with external cooling The theoretical amount of hydrogen (0.26 M) is consumed

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

Procedure: A mixture of methyl 2- methyl-5-nitrobenzyl ether (12 g. 0.066 M), methoxyacetone [20 g (used as solvent)], 2-naphthalenesulfonic acid (0.3 g) and 5% Pt/C (0.7 g) is shaken on a Parr hydrogenator maintaining the temperature below 40° with external cooling. The theoretical amount of hydrogen (0.26 M) is consumed and further uptake ceases after 2 hours. maintaining the temperature below 40° with external cooling The theoretical amount of hydrogen (0.26 M) is consumed

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

Procedure: A solution consisting of 23.8 g of N-(3,4-dimethoxybenzyl)-N-(2-methoxy-1-methylethyl)amine (prepared by condensing 3,4-dimethoxybenzylamine and methoxy acetone and hydrogenating the condensation product), 80 ml of toluene, and 20 ml of water in which 4 g of solid sodium hydroxide were dissolved is prepared and cooled down to -10° to -15°. Another solution of 14.7 g of dichloroacetylchloride in 10 ml of toluene is then added dropwise thereto while stirring. The mixture is stirred for one hour after all the dichloro-acetylchloride is added and the poured into 1 l of ice-water. The organic layer that formed was then extracted with ether, washed with diluted hydrochloric acid and twice with water, dried and concentrated. The residue crystallises spontaneously and yields 30.9 g of raw product melting at 62°-63°. After recrystalliation from a toluene/pentane mixture one obtained 21.3 g of pure title product melting at 75°-76°. were dissolved is prepared cooled down to -10° to -15° is added The organic layer that formed was then extracted with ether washed with diluted hydrochloric acid and twice with water dried concentrated The residue crystallises spontaneously yields 30.9 g of raw product melting at 62°-63°

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

Procedure: A solution consisting of 23.8 g of N-(3,4-dimethoxybenzyl)-N-(2-methoxy-1-methylethyl)amine (prepared by condensing 3,4-dimethoxybenzylamine and methoxy acetone and hydrogenating the condensation product), 80 ml of toluene, and 20 ml of water in which 4 g of solid sodium hydroxide were dissolved is prepared and cooled down to -10° to -15°. Another solution of 14.7 g of dichloroacetylchloride in 10 ml of toluene is then added dropwise thereto while stirring. The mixture is stirred for one hour after all the dichloro-acetylchloride is added and the poured into 1 l of ice-water. The organic layer that formed was then extracted with ether, washed with diluted hydrochloric acid and twice with water, dried and concentrated. The residue crystallises spontaneously and yields 30.9 g of raw product melting at 62°-63°. After recrystalliation from a toluene/pentane mixture one obtained 21.3 g of pure title product melting at 75°-76°. were dissolved is prepared cooled down to -10° to -15° is added The organic layer that formed was then extracted with ether washed with diluted hydrochloric acid and twice with water dried concentrated The residue crystallises spontaneously yields 30.9 g of raw product melting at 62°-63°

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

Procedure: Methoxyacetone (5.22 mL, 56.8 mmol) was added dropwise to a cold (0° C.), stirred solution of sodium ethoxide (21% in EtOH, 20.2 g, 62.4 mmol) and EtOH (50 mL), under an argon atmosphere. The reaction mixture was stirred for 30 min at 0° C. Then, diethyl oxalate (7.71 mL, 56.8 mmol) was added. The reaction mixture was allowed to warm to rt, stirred for 16 h, quenched by addition of 1N HCl (75 mL), and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The crude material was purified by silica gel column chromatography (hexane/EtOAc 5-10%) to afford the title compound (3.21 g) as a yellow oil. tR: 0.70 min (LC-MS 2); ESI-MS: 189.1 [M+H]+ (LC-MS 2); Rf=0.25 (hexane/EtOAc 1:1, CPS staining). to warm to rt stirred for 16 h quenched by addition of 1N HCl (75 mL) extracted with CH2Cl2 The combined organic layers were dried over Na2SO4 the solvent was evaporated off under reduced pressure The crude material was purified by silica gel column chromatography (hexane/EtOAc 5-10%)

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

Procedure: Under nitrogen atmosphere sodium (1.61 g, 70.0 mmol) was dissolved in small pieces in a flask containing dry ethanol (150 ml). Diethyl oxalate (8.15 ml, 60 mmol) and methoxyacetone (5.52 ml, 60.0 mmol) were added with a syringe. The resulting mixture was stirred at RT for 1 h. The flask was put in an ice bath and into it a mixture of sulphuric acid and ice water was added dropwise. The resulting precipitate was filtered and washed with DCM. The ethanol/DCM filtrate was evaporated. The residue was dissolved in DCM, extracted with brine and the DCM phase dried with Na2SO4, filtered and evaporated. The product was purified with flash chromatography. 1H-NMR (400 MHz; DMSO-d6): δ 1.28 (t, 3H), 3.34 (s, 3H), 4.19-4.23 (m, 2H), 4.27 (q, 2H). The flask was put in an ice bath and into it was added dropwise The resulting precipitate was filtered washed with DCM The ethanol/DCM filtrate was evaporated The residue was dissolved in DCM extracted with brine the DCM phase dried with Na2SO4 filtered evaporated The product was purified with flash chromatography

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

Procedure: Under nitrogen atmosphere sodium (1.61 g, 70.0 mmol) was dissolved in small pieces in a flask containing dry ethanol (150 ml). Diethyl oxalate (8.15 ml, 60 mmol) and methoxyacetone (5.52 ml, 60.0 mmol) were added with a syringe. The resulting mixture was stirred at RT for 1 h. The flask was put in an ice bath and into it a mixture of sulphuric acid and ice water was added dropwise. The resulting precipitate was filtered and washed with DCM. The ethanol/DCM filtrate was evaporated. The residue was dissolved in DCM, extracted with brine and the DCM phase dried with Na2SO4, filtered and evaporated. The product was purified with flash chromatography. 1H-NMR (400 MHz; DMSO-d6): δ 1.28 (t, 3H), 3.34 (s, 3H), 4.19-4.23 (m, 2H), 4.27 (q, 2H). The flask was put in an ice bath and into it was added dropwise The resulting precipitate was filtered washed with DCM The ethanol/DCM filtrate was evaporated The residue was dissolved in DCM extracted with brine the DCM phase dried with Na2SO4 filtered evaporated The product was purified with flash chromatography

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

Procedure: A mixture of methyl 2-methyl-5-nitrobenzyl ether (12 g, 0.066 M), methoxyacetone [20 g (used as solvent)], 2-naphthalenesulfonic acid (0.3 g) and 5% Pt/C (0.7 g) is shaken on a Parr hydrogenator maintaining the temperature below 40° with external cooling. The theoretical amount of hydrogen (0.26 M) is consumed and further uptake ceases after 2 hours. maintaining the temperature below 40° with external cooling The theoretical amount of hydrogen (0.26 M) is consumed

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

Procedure: A mixture of methyl 2-methyl-5-nitrobenzyl ether (12 g, 0.066 M), methoxyacetone [20 g (used as solvent)], 2-naphthalenesulfonic acid (0.3 g) and 5% Pt/C (0.7 g) is shaken on a Parr hydrogenator maintaining the temperature below 40° with external cooling. The theoretical amount of hydrogen (0.26 M) is consumed and further uptake ceases after 2 hours. maintaining the temperature below 40° with external cooling The theoretical amount of hydrogen (0.26 M) is consumed

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

Procedure: A solution of 1-methoxypropan-2-one (20.3 g, 231 mmol) in 200 mL of MeOH was added to a 250 mL round-bottom flask. The flask was then immersed in an ice-water bath. Br2 was added dropwise to the reaction mixture through an addition funnel. After the addition, the addition funnel was rinsed with 50 mL MeOH, and the reaction mixture was stirred for 20 minutes at 0° C. The ice-water bath was then removed, and the reaction mixture was stirred for two more hours. Thiourea (18 g, 231 mmol) was then added to the reaction mixture, and the reaction was heated at reflux overnight. The reaction was concentrated, and saturated sodium bicarbonate and solid sodium carbonate were used to adjust the pH to 8-9. The resulting mixture was then extracted three times with 200 mL portions of EtOAc. The organic layers were concentrated and then purified by recrystallization to give 4-(methoxymethyl)thiazol-2-amine (11 g, 33% yield over two steps). MS m/z: 145 (M+1). The flask was then immersed in an ice-water bath After the addition the addition funnel was rinsed with 50 mL MeOH The ice-water bath was then removed the reaction mixture was stirred for two more hours the reaction was heated at reflux overnight The reaction was concentrated The resulting mixture was then extracted three times with 200 mL portions of EtOAc The organic layers were concentrated purified by recrystallization