反应详情

Part B: To the THF solution of crude 1-[N-[(1,3-benzodioxol-5-yl)sulfonyl]-N-(2-methylpropyl)amino]-3(S)-[bis(phenylmethyl)amino]-4-phenyl-2(R)-butanol was added water (500 mL) followed by methane sulfonic acid (531 g, 5.5 moles). The solution was stirred to insure complete mixing and added to a 5 gallon autoclave. Pearlman's catalyst (200 g of 20% Pd(OH)2 on C/50% water) was added to the autoclave with the aid of THF (500 mL). The reactor was purged four times with nitrogen and four times with hydrogen. The reactor was charged with 60 psig of hydrogen and stirring at 450 rpm started. After 16 hours, HPLC analysis indicated that a small amount of the mono-benzyl intermediate was still present Additional catalyst (50 g) was added and the reaction was allowed to run overnight. The solution was then filtered through celite (500 g) to remove the catalyst and concentrated under vacuum in five portions. To each portion, toluene (500 mL) was added and removed under vacuum to azeotropically removed residual water. The resulting solid was divided into three portions and each washed with methyl t-butyl ether (2 L) and filtered. The residual solvent was removed at room temperature in a vacuum oven at less than 1 torr to yield the 2714 g of the expected salt.

1. additionto insure complete mixing
2. additionadded to a 5 gallon autoclave
3. customThe reactor was purged four times with nitrogen and four times with hydrogen
4. additionThe reactor was charged with 60 psig of hydrogen
5. stirringstirring at 450 rpm
6. additionwas added
7. waitto run overnight
8. filtrationThe solution was then filtered through celite (500 g)
9. customto remove the catalyst
10. concentrationconcentrated under vacuum in five portions
11. additionTo each portion, toluene (500 mL) was added
12. customremoved under vacuum to azeotropically removed residual water
13. washeach washed with methyl t-butyl ether (2 L)
14. filtrationfiltered
15. customThe residual solvent was removed at room temperature in a vacuum oven at less than 1 torr