N-hydroxy-N-methylbenzamide

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

Procedure: 10.0 g of N-methylhydroxylamine hydrochloride was added to 100 ml of tetrahydrofuran. 19.8 g of pyridine was added to the mixture. A solution of 16.8 g of benzoyl chloride in 100 ml of tetrahydrofuran was dropwise added to the mixture under stirring at room temperature over 1 hr. The stirring was continued at room temperature for additional 8 hr. to conduct the reaction. 50 ml of dilute hydrochloric acid was added thereto and then tetrahydrofuran was removed under reduced pressure. After extraction with ethyl acetate, the extract was dehydrated over anhydrous magnesium sulfate. Ethyl acetate was removed under reduced pressure. The resultant crude product was purified according to column chromatography (packing: silica gel, developer: ethyl acetate/hexane) to obtain 8.5 g of N-benzoyl-N-methylhydroxylamine as an oil having a melting point of 20° C. or below. 130 ml of tetrahydrofuran was added to 7.6 g of N-benzoyl-N-methylhydroxylamine and 12.6 g of 4-vinyl-1-naphthalenesulfonyl chloride. A solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added thereto under stirring over 2 hr. while the mixture was cooled so that the temperature of the solution was below 25° C. After conducting the reaction at 15° to 25° C. for additional 2 hr., the reaction solution was poured into 700 ml of water and the precipitate thus formed was collected by filtration. After recrystallization from acetonitrile, 12.8 g of o-(4-vinyl-1-naphthalenesulfonyl)-N-benzoyl-N-methylhydroxylamine was obtained. while the mixture was cooled so that the temperature of the solution was below 25° C the reaction at 15° to 25° C. for additional 2 hr the precipitate thus formed was collected by filtration After recrystallization from acetonitrile

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

Procedure: 10.0 g of N-methylhydroxylamine hydrochloride was added to 100 ml of tetrahydrofuran. 19.8 g of pyridine was added to the mixture. A solution of 16.8 g of benzoyl chloride in 100 ml of tetrahydrofuran was dropwise added to the mixture under stirring at room temperature over 1 hr. The stirring was continued at room temperature for additional 8 hr. to conduct the reaction. 50 ml of dilute hydrochloric acid was added thereto and then tetrahydrofuran was removed under reduced pressure. After extraction with ethyl acetate, the extract was dehydrated over anhydrous magnesium sulfate. Ethyl acetate was removed under reduced pressure. The resultant crude product was purified according to column chromatography (packing: silica gel, developer: ethyl acetate/hexane) to obtain 8.5 g of N-benzoyl-N-methylhydroxylamine as an oil having a melting point of 20° C. or below. 130 ml of tetrahydrofuran was added to 7.6 g of N-benzoyl-N-methylhydroxylamine and 12.6 g of 4-vinyl-1-naphthalenesulfonyl chloride. A solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added thereto under stirring over 2 hr. while the mixture was cooled so that the temperature of the solution was below 25° C. After conducting the reaction at 15° to 25° C. for additional 2 hr., the reaction solution was poured into 700 ml of water and the precipitate thus formed was collected by filtration. After recrystallization from acetonitrile, 12.8 g of o-(4-vinyl-1-naphthalenesulfonyl)-N-benzoyl-N-methylhydroxylamine was obtained. The stirring was continued at room temperature for additional 8 hr the reaction tetrahydrofuran was removed under reduced pressure After extraction with ethyl acetate Ethyl acetate was removed under reduced pressure The resultant crude product was purified

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

Procedure: 10.0 g of N-methylhydroxylamine hydrochloride was added to 100 ml of tetrahydrofuran. 19.8 g of pyridine was added to the mixture. A solution of 16.8 g of benzoyl chloride in 100 ml of tetrahydrofuran was dropwise added to the mixture under stirring at room temperature over 1 hr. The stirring was continued at room temperature for additional 8 hr. to conduct the reaction. 50 ml of dilute hydrochloric acid was added thereto and then tetrahydrofuran was removed under reduced pressure. After extraction with ethyl acetate, the extract was dehydrated over anhydrous magnesium sulfate. Ethyl acetate was removed under reduced pressure. The resultant crude product was purified according to column chromatography (packing: silica gel, developer: ethyl acetate/hexane) to obtain 8.5 g of N-benzoyl-N-methylhydroxylamine as an oil having a melting point of 20° C. or below. 130 ml of tetrahydrofuran was added to 7.6 g of N-benzoyl-N-methylhydroxylamine and 12.6 g of 4-vinyl-1-naphthalenesulfonyl chloride. A solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added thereto under stirring over 2 hr. while the mixture was cooled so that the temperature of the solution was below 25° C. After conducting the reaction at 15° to 25° C. for additional 2 hr., the reaction solution was poured into 700 ml of water and the precipitate thus formed was collected by filtration. After recrystallization from acetonitrile, 12.8 g of o-(4-vinyl-1-naphthalenesulfonyl)-N-benzoyl-N-methylhydroxylamine was obtained. while the mixture was cooled so that the temperature of the solution was below 25° C the reaction at 15° to 25° C. for additional 2 hr the precipitate thus formed was collected by filtration After recrystallization from acetonitrile

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

Procedure: 10.0 g of N-methylhydroxylamine hydrochloride was added to 100 ml of tetrahydrofuran. 19.8 g of pyridine was added to the mixture. A solution of 16.8 g of benzoyl chloride in 100 ml of tetrahydrofuran was dropwise added to the mixture under stirring at room temperature over 1 hr. The stirring was continued at room temperature for additional 8 hr. to conduct the reaction. 50 ml of dilute hydrochloric acid was added thereto and then tetrahydrofuran was removed under reduced pressure. After extraction with ethyl acetate, the extract was dehydrated over anhydrous magnesium sulfate. Ethyl acetate was removed under reduced pressure. The resultant crude product was purified according to column chromatography (packing: silica gel, developer: ethyl acetate/hexane) to obtain 8.5 g of N-benzoyl-N-methylhydroxylamine as an oil having a melting point of 20° C. or below. 130 ml of tetrahydrofuran was added to 7.6 g of N-benzoyl-N-methylhydroxylamine and 12.6 g of 4-vinyl-1-naphthalenesulfonyl chloride. A solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added thereto under stirring over 2 hr. while the mixture was cooled so that the temperature of the solution was below 25° C. After conducting the reaction at 15° to 25° C. for additional 2 hr., the reaction solution was poured into 700 ml of water and the precipitate thus formed was collected by filtration. After recrystallization from acetonitrile, 12.8 g of o-(4-vinyl-1-naphthalenesulfonyl)-N-benzoyl-N-methylhydroxylamine was obtained. The stirring was continued at room temperature for additional 8 hr the reaction tetrahydrofuran was removed under reduced pressure After extraction with ethyl acetate Ethyl acetate was removed under reduced pressure The resultant crude product was purified

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

Procedure: The n-methyl hydroxylamine-HCl and m-pyrol were combined in a 250 milliliter (ml) round bottomed flask, cooled in an ice bath, and allowed to mix until most of the salt dissolved. The benzoyl chloride was slowly added over 15 minutes and allowed to stir for 1 hour. The water was then added and the product extracted three times with ethyl acetate. The ethyl acetate was evaporated from the product, and the product dissolved in 200 ml of 5% NaOH. The product was then extracted three times with 100 ml methylene chloride. The aqueous layer was acidified with H2S04 to a pH of 6 and then extracted three times with 100 ml of ethyl acetate. The organic layer was dried with MgS04 and silica gel, and evaporated to dryness yielding n-methylbenzohydroxamic acid. cooled in an ice bath to mix until most of the salt dissolved the product extracted three times with ethyl acetate The ethyl acetate was evaporated from the product the product dissolved in 200 ml of 5% NaOH The product was then extracted three times with 100 ml methylene chloride extracted three times with 100 ml of ethyl acetate The organic layer was dried with MgS04 and silica gel evaporated to dryness

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

Procedure: The n-methyl hydroxylamine-HCl and m-pyrol were combined in a 250 milliliter (ml) round bottomed flask, cooled in an ice bath, and allowed to mix until most of the salt dissolved. The benzoyl chloride was slowly added over 15 minutes and allowed to stir for 1 hour. The water was then added and the product extracted three times with ethyl acetate. The ethyl acetate was evaporated from the product, and the product dissolved in 200 ml of 5% NaOH. The product was then extracted three times with 100 ml methylene chloride. The aqueous layer was acidified with H2S04 to a pH of 6 and then extracted three times with 100 ml of ethyl acetate. The organic layer was dried with MgS04 and silica gel, and evaporated to dryness yielding n-methylbenzohydroxamic acid. cooled in an ice bath to mix until most of the salt dissolved the product extracted three times with ethyl acetate The ethyl acetate was evaporated from the product the product dissolved in 200 ml of 5% NaOH The product was then extracted three times with 100 ml methylene chloride extracted three times with 100 ml of ethyl acetate The organic layer was dried with MgS04 and silica gel evaporated to dryness

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

Procedure: The n-methyl hydroxylamine-HCl and m-pyrol were combined in a 250 milliliter (ml) round bottomed flask, cooled in an ice bath, and allowed to mix until most of the salt dissolved. The benzoyl chloride was slowly added over 15 minutes and allowed to stir for 1 hour. The water was then added and the product extracted three times with ethyl acetate. The ethyl acetate was evaporated from the product, and the product dissolved in 200 ml of 5% NaOH. The product was then extracted three times with 100 ml methylene chloride. The aqueous layer was acidified with H2S04 to a pH of 6 and then extracted three times with 100 ml of ethyl acetate. The organic layer was dried with MgS04 and silica gel, and evaporated to dryness yielding n-methylbenzohydroxamic acid. cooled in an ice bath to mix until most of the salt dissolved the product extracted three times with ethyl acetate The ethyl acetate was evaporated from the product the product dissolved in 200 ml of 5% NaOH The product was then extracted three times with 100 ml methylene chloride extracted three times with 100 ml of ethyl acetate The organic layer was dried with MgS04 and silica gel evaporated to dryness

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

Procedure: N-Tosyloxy-N-methylbenzamide was prepared by the following procedure. To a flask equipped with a stirrer were added N-hydroxy-N-methylbenzamide (1.39 g, 0.010 mol) from above, p-toluenesulfonyl chloride (1.91 g, 0.010 mol), 25 mL of THF and 2 mL of triethylamine. After 30 min at 0° followed by 1 h at room temperature, the reaction mixture was diluted with 50 mL of methylene chloride, and the solution was washed with water (4×50 mL) and dried. Evaporation of the solvent left 2.84 g of a golden oil which soon crystallized. Recrystallization from methylene chloride-hexane gave 2.04 g (69.4%) of fluffy white N-tosyloxy-N-methylbenzamide: mp 98°-99.5°; nmr (CDCl3) 7.8-7.0 (A2B2 and singlet at 7.36, 9H), 3.53 (s, 3H), 2.38 (s, 3H); ir (KBr) 1684 (vs), 1370 (s), 1180 (s), 1170 (s), 880 (m), 805 (m), 735 (m), 695 (s), 651 (m), 540 (s): uv (CH3CN) 227 (19,200), 265 (sh, 2020), 273 nm (sh, 1500); mass spectrum 305.0720 (calcd for C15H15O4NS: m+, 305.0720). Anal. Calcd for C15H15O4NS: C, 59.00; H, 4.95; N, 4.59; S, 20.96; O, 10.50. Found: C, 58.87, 58.75; H, 4.98, 5.02; N, 4.52, 4.43. N-Tosyloxy-N-methylbenzamide was prepared by the following procedure To a flask equipped with a stirrer the solution was washed with water (4×50 mL) dried Evaporation of the solvent left 2.84 g of a golden oil which soon crystallized Recrystallization from methylene chloride-hexane

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

Procedure: To a flask equipped with a stirrer and a heating mantle were added N-methyl-N-benzoyloxybenzamide (29.2 g, 0.119 mol) from above, 100 mL of water, and 10 g of sodium hydroxide. The mixture was stirred well and heated to 70°. A clear solution was obtained in 30 min. After a total of 45 min the solution was cooled and concentrated hydrochloric acid was added to bring the solution to pH 7. The mixture was extracted with methylene chloride, and the organic layer was dried, first with magnesium sulfate and then with 4 A molecular sieves. Evaporation of the solvent gave 14.7 g (81%) of colorless, liquid, N-hydroxy-N-methylbenzamide; nmr (CDCl3) 9.67 (broad s, CH, 1H), 7.7-7.1 (m, 5H), 3.20 (s, 3H). Attempts to vacuum distill the product were unsuccessful because of thermal decomposition. To a flask equipped with a stirrer heated to 70° A clear solution was obtained in 30 min After a total of 45 min the solution was cooled The mixture was extracted with methylene chloride the organic layer was dried, first with magnesium sulfate Evaporation of the solvent

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

Procedure: 130 ml of tetrahydrofuran was added to a mixture of 7.6 g of N-benzoyl-N-methylhydroxylamine and 6.3 g of vinylsulfonyl chloride and a solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added to the mixture over 2 hours with stirring while cooling the mixture so that the temperature was maintained at 25° C. or less. The reaction was continued for additional 2 hours at a temperature ranging from 15° to 25° C. and then the same procedures used in Preparation Example 4 were repeated to give 9.2 g of o-vinylsulfonyl-N-benzoyl-N-methylhydroxylamine. while cooling the mixture so that the temperature was maintained at 25° C. or less ranging from 15° to 25° C. the same procedures used in Preparation Example 4

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

Procedure: 10.0 g of N-methylhydroxylamine hydrochloride was added to 100 ml of tetrahydrofuran and 19.8 g of pyridine was added to the mixture. To the resulting mixture, there was dropwise added a solution of 16.8 g of benzoyl chloride in 100 ml of tetrahydrofuran at room temperature over one hour with stirring. The stirring was continued for additional 8 hours to proceed the reaction. After addition of 50 ml of dilute hydrochloric acid, the tetrahydrofuran was removed in vacuo and the remaining solution was extracted with ethyl acetate. The resultant extract was dried over anhydrous magnesium sulfate and then the ethyl acetate was removed under reduced pressure. The crude product obtained was purified by column chromatography (packed material: silica gel; eluent: ethyl acetate/hexane) to give 8.5 g of N-benzoyl-N-methylhydroxylamine as an oil having a melting point of not more than 20° C. was added to the mixture the reaction the tetrahydrofuran was removed in vacuo the remaining solution was extracted with ethyl acetate The resultant extract was dried over anhydrous magnesium sulfate the ethyl acetate was removed under reduced pressure The crude product obtained was purified by column chromatography (packed material: silica gel; eluent: ethyl acetate/hexane)

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

Procedure: 130 ml of tetrahydrofuran was added to a mixture of 7.6 g of N-benzoyl-N-methylhydroxylamine and 6.3 g of vinylsulfonyl chloride and a solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added to the mixture over 2 hours with stirring while cooling the mixture so that the temperature was maintained at 25 ° C. or less. The reaction was continued for additional 2 hours at a temperature ranging from 15° to 25 ° C. and then the same procedures used in Preparation Example 4 were repeated to give 9.2 g of o-vinylsulfonyl-N-benzoyl-N-methylhydroxylamine. while cooling the mixture so that the temperature was maintained at 25 ° C. or less ranging from 15° to 25 ° C. the same procedures used in Preparation Example 4