反应详情

Crude 1-[N-[(1,3-benzodioxol-5-yl)sulfonyl]-N-(2-methylpropyl)amino]-3(S)-[bis(phenylmethyl)amino]-4-phenyl-2(R)-butanol (6.2 g, 0.010 moles) was dissolved in methanol (40 mL). Methanesulfonic acid (0.969 g, 0.010 moles) and water (5 mL) were then added to the solution. The mixture was placed in a 500 mL Parr hydrogenation bottle containing 20% Pd(OH)2 on carbon (255 mg, 50% water content). The bottle was placed in the hydrogenator and purged 5 times with nitrogen and 5 times with hydrogen. The reaction was allowed to proceed at 35° C. with 63 PSI hydrogen pressure for 18 hours. Additional catalyst (125 mg) was added and, after purging, the hydrogenation continued for and additional 20 hours. The mixture was filtered through celite which was washed with methanol (2×10 mL). Approximately one third of the methanol was removed under reduced pressure. The remaining methanol was removed by aziotropic distillation with toluene at 80 torr. Toluene was added in 15, 10, 10 and 10 mL portions. The product crystallized from the mixture and was filtered and washed twice with 10 mL portions of toluene. The solid was dried at room temperature at 1 torr for 6 hours to yield the amine salt (4.5 g, 84%). HPLC/MS (electrospray) was consistent with the desired product (m/z 421 [M+H]+).

1. custompurged 5 times with nitrogen and 5 times with hydrogen
2. additionAdditional catalyst (125 mg) was added
3. customafter purging
4. customadditional 20 hours
5. filtrationThe mixture was filtered through celite which
6. washwas washed with methanol (2×10 mL)
7. customApproximately one third of the methanol was removed under reduced pressure
8. customThe remaining methanol was removed by aziotropic distillation with toluene at 80 torr
9. additionToluene was added in 15, 10, 10 and 10 mL portions
10. customThe product crystallized from the mixture
11. filtrationwas filtered
12. washwashed twice with 10 mL portions of toluene
13. customThe solid was dried at room temperature at 1 torr for 6 hours