反应详情

1,1′-carbonyidiimidazole (27.66 kg, 170.58 mol) was added to ethyl acetate (314.3 kg) with stirring to give 3-(S)-tetrahydrofuryl imidazole-1-carboxylate. (S)-3-hydroxytetrahydrofuran (157 kg, 178.19 mol) was added over 30 minutes, washed in with ethyl acetate (9.95 kg), then the mixture was stirred for a further hour. (2R,3S)-N-(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-nitrobenzene sulphonamide hydrochloride (65.08 kg, 142.10 mol) was added and the mixture heated to reflux for approximately 22 hours. The solution was cooled slightly, and denatured ethanol (98 l) was added. The solution was stirred at 60° C. for 10 minutes then cooled and the product allowed to crystallise. The mixture was cooled to <10° C. and stirred for 2 hours. The product was isolated by filtration, washed with denatured ethanol (33 l) and dried at approximately 50° C., under vacuum to give (3S)-tetrahydro-3-furyl N-[(1S,2R)-1-benzyl-2-hydroxy-3-(N-isobutyl-4-nitrobenzene sulphonamido)propyl]carbamate in a yield of 82% of theory.

1. washwashed in with ethyl acetate (9.95 kg)
2. temperaturethe mixture heated
3. temperatureto reflux for approximately 22 hours
4. temperatureThe solution was cooled slightly
5. stirringThe solution was stirred at 60° C. for 10 minutes
6. temperaturethen cooled
7. customto crystallise
8. temperatureThe mixture was cooled to <10° C.
9. stirringstirred for 2 hours
10. customThe product was isolated by filtration
11. washwashed with denatured ethanol (33 l)
12. customdried at approximately 50° C., under vacuum