N,N-bis(2-chloroethyl)methanesulfonamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 14.3 ml (185 mmol) of methanesulfonyl chloride are added slowly to a solution of 15 g (84 mmol) of commercial bis(2-chloroethylamine) hydrochloride and 26 ml (185 mmol) of triethylamine in 200 ml of dichloromethane and 70 ml of tetrahydrofuran previously stirred for 15 min and then filtered in order to remove the triethylammonium chloride. The reaction medium is then stirred at ambient temperature for 18 h, extracted with dichloromethane, and washed with water. The organic phase is dried over magnesium sulfate, filtered and evaporated. The residue obtained is washed with diisopropyl ether, filtered and then dried under vacuum. 15.3 g (82%) of N,N-bis-(2-chloroethyl)methanesulfonamide are obtained in the form of a solid. filtered in order to remove the triethylammonium chloride The reaction medium is then stirred at ambient temperature for 18 h extracted with dichloromethane washed with water The organic phase is dried over magnesium sulfate filtered evaporated The residue obtained is washed with diisopropyl ether filtered dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a Schlenk tube, a solution of 5 g (20 mmol) of methyl (S)-2-amino-3-tert-butoxycarbonylaminopropanoate hydrochloride and 4.3 g (20 mmol) of N,N-bis(2-chloroethyl)methanesulfonamide in 65 ml of N,N-diisopropylethylamine is heated at 127° C. with vigorous stirring for 18 h. After the addition of water, the product is extracted with ethyl acetate. The organic phases are combined, washed with water, dried over magnesium sulfate, filtered and concentrated under vacuum. The crude product obtained is purified by chromatography on silica gel, elution being carried out with a 50/50 heptane/ethyl acetate mixture. 3.3 g (46%) of methyl (S)-3-tert-butoxycarbonylamino-2-(4-methanesulfonylpiperazin-1-yl)propanoate are obtained in the form of a white solid. the product is extracted with ethyl acetate washed with water dried over magnesium sulfate filtered concentrated under vacuum The crude product obtained is purified by chromatography on silica gel, elution

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 8.6 ml (62 mmol) of triethylamine are added to a solution of 5 g (28 mmol) of bis(2-chloroethyl)amine hydrochloride in 60 ml of dichloromethane. The triethylammonium chloride salts precipitate and are filtered off. 2.4 ml (31 mmol) of methylsulfonyl chloride are then added to the filtrate obtained, and the reaction medium is stirred at ambient temperature for 3 h. After the addition of water, the product is extracted with dichloromethane. The organic phase is washed with water, dried over magnesium sulfate, filtered and concentrated. 5.8 g (94%) of N,N-bis(2-chloroethyl)methanesulfonamide are obtained in the form of a beige solid. The triethylammonium chloride salts precipitate are filtered off obtained the product is extracted with dichloromethane The organic phase is washed with water dried over magnesium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 8.6 ml (62 mmol) of triethylamine are added to a solution of 5 g (28 mmol) of bis(2-chloroethyl)amine hydrochloride in 60 ml of dichloromethane. The triethylammonium chloride salts precipitate and are filtered off. 2.4 ml (31 mmol) of methylsulfonyl chloride are then added to the filtrate obtained, and the reaction medium is stirred at ambient temperature for 3 h. After the addition of water, the product is extracted with dichloromethane. The organic phase is washed with water, dried over magnesium sulfate, filtered and concentrated. 5.8 g (94%) of N,N-bis(2-chloroethyl)methanesulfonamide are obtained in the form of a beige solid. The triethylammonium chloride salts precipitate are filtered off obtained the product is extracted with dichloromethane The organic phase is washed with water dried over magnesium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 6 g (23.6 mmol) of methyl (R)-2-amino-3-tert-butoxycarbonylaminopropanoate hydrochloride and 5.2 g (23.6 mmol) of N,N-bis(2-chloroethyl)methanesulphonamide in 80 ml of N,N-diisopropylethylamine is heated at 125° C. with vigorous stirring for 18 h. After addition of water, the product is extracted with ethyl acetate. The organic phases are combined, washed with water, dried over magnesium sulphate, filtered and concentrated under vacuum. The crude product obtained is purified by chromatography over silica gel eluted with a 5/5 heptane/ethyl acetate mixture. 3.8 g (44%) of methyl (R)-3-tert-butoxycarbonylamino-2-(4-methanesulphonylpiperazin-1-yl)propanoate are obtained in the form of a white solid. the product is extracted with ethyl acetate washed with water dried over magnesium sulphate filtered concentrated under vacuum The crude product obtained is purified by chromatography over silica gel eluted with a 5/5 heptane/ethyl acetate mixture

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 17 ml (123.2 mmol) of triethylamine are added to a solution of 10 g (56 mmol) of bis(2-chloroethyl)amine hydrochloride in 100 ml of dichloromethane. After filtration of the salts, 4.6 ml (58.8 mmol) of methanesulphonyl chloride are added to the filtrate obtained and the reaction medium is stirred at ambient temperature for 3 h. After addition of water, the product is extracted with dichloromethane. The organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated. 11.6 g (94%) of N,N-bis(2-chloroethyl)methanesulphonamide are obtained in the form of a beige solid. are added to the filtrate obtained the product is extracted with dichloromethane The organic phase is washed with water dried over magnesium sulphate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 17 ml (123.2 mmol) of triethylamine are added to a solution of 10 g (56 mmol) of bis(2-chloroethyl)amine hydrochloride in 100 ml of dichloromethane. After filtration of the salts, 4.6 ml (58.8 mmol) of methanesulphonyl chloride are added to the filtrate obtained and the reaction medium is stirred at ambient temperature for 3 h. After addition of water, the product is extracted with dichloromethane. The organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated. 11.6 g (94%) of N,N-bis(2-chloroethyl)methanesulphonamide are obtained in the form of a beige solid. are added to the filtrate obtained the product is extracted with dichloromethane The organic phase is washed with water dried over magnesium sulphate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 5 g (20 mmol) of methyl (S)-2-amino-3-tert-butoxycarbonylaminopropanoate hydrochloride and 4.3 g (20 mmol) of N,N-bis(2-chloroethyl)methanesulphonamide in 65 ml of N,N-diisopropylethylamine is heated at 127° C. with vigorous stirring for 18 h. After addition of water, the product is extracted with ethyl acetate. The organic phases are combined, washed with water, dried over magnesium sulphate, filtered and concentrated under vacuum. The crude product obtained is purified by chromatography over silica gel eluted with a 50/50 heptane/ethyl acetate mixture. 3.3 g (46%) of methyl (S)-3-tert-butoxycarbonylamino-2-(4-methanesulphonylpiperazin-1-yl)propanoate are obtained in the form of a white solid. the product is extracted with ethyl acetate washed with water dried over magnesium sulphate filtered concentrated under vacuum The crude product obtained is purified by chromatography over silica gel eluted with a 50/50 heptane/ethyl acetate mixture

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 8.6 ml (62 mmol) of triethylamine are added to a solution of 5 g (28 mmol) of bis(2-chloroethyl)amine hydrochloride in 60 ml of dichloromethane. After filtration of the salts, 2.4 ml (31 mmol) of methanesulphonyl chloride are added to the filtrate obtained and the reaction medium is stirred at ambient temperature for 3 h. After addition of water, the product is extracted with dichloromethane. The organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated. 5.8 g (94%) of N,N-bis(2-chloroethyl)methanesulphonamide are obtained in the form of a beige solid. are added to the filtrate obtained the product is extracted with dichloromethane The organic phase is washed with water dried over magnesium sulphate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 14.3 ml (185 mmol) of methanesulfonyl chloride are added slowly to a solution of 15 g (84 mmol) of commercial bis(2-chloroethylamine) hydrochloride and 26 ml (185 mmol) of triethylamine in 200 ml of dichloromethane and 70 ml of tetrahydrofuran previously stirred for 15 min and then filtered in order to remove the triethylammonium chloride. The reaction medium is then stirred at ambient temperature for 18 h, extracted with dichloromethane, and washed with water. The organic phase is dried over magnesium sulfate, filtered and evaporated. The residue obtained is washed with diisopropyl ether, filtered and then dried under vacuum. 15.3 g (82%) of N,N-bis-(2-chloroethyl)methanesulfonamide are obtained in the form of a solid. filtered in order to remove the triethylammonium chloride The reaction medium is then stirred at ambient temperature for 18 h extracted with dichloromethane washed with water The organic phase is dried over magnesium sulfate filtered evaporated The residue obtained is washed with diisopropyl ether filtered dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 14.3 ml (185 mmol) of methanesulfonyl chloride are added slowly to a solution of 15 g (84 mmol) of commercial bis(2-chloroethylamine) hydrochloride and 26 ml (185 mmol) of triethylamine in 200 ml of dichloromethane and 70 ml of tetrahydrofuran previously stirred for 15 min and then filtered in order to remove the triethylammonium chloride. The reaction medium is then stirred at ambient temperature for 18 h, extracted with dichloromethane, and washed with water. The organic phase is dried over magnesium sulfate, filtered and evaporated. The residue obtained is washed with diisopropyl ether, filtered and then dried under vacuum. 15.3 g (82%) of N,N-bis-(2-chloroethyl)methanesulfonamide are obtained in the form of a solid. filtered in order to remove the triethylammonium chloride The reaction medium is then stirred at ambient temperature for 18 h extracted with dichloromethane washed with water The organic phase is dried over magnesium sulfate filtered evaporated The residue obtained is washed with diisopropyl ether filtered dried under vacuum