反应详情

The entirety of N-(2-((1S,2R,4R)-4-amino-2-((S)-1-hydroxy-2-methylpropyl)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide te prepared in previous Step (1 eq) in CH2Cl2 (20 mL). The resultant solution was charged with acetone (10 eq) and stirred at RT for 10 min before sodium cyanoborohydride (2 eq) was added in one portion. The reaction was stirred at RT for 10 h and then charged successively with formaldehyde (10 eq in 37 wt % aq soln) and sodium cyanoborohydride (2 eq). The reaction was stirred for another 9 h at RT and then quenched with sat. NaHCO3. The aqueous mixture was extracted with EtOAc (40 mL, then 2×40 mL). The organic extracts were combined, washed with brine (30 mL), dried (MgSO4), filtered, and concentrated in vacuo. After the resulting oil stood, some paraformaldehyde-related products solidified; these were removed by dissolving the mixture in a minimal volume of EtOAc and filtering. Subsequent concentration provided N-(2-((1S,2R,4R)-2-((S)-1-hydroxy-2-methylpropyl)-4-(isopropyl(methyl)amino)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide. MS found: (M+H)+=472.

1. additionwas added in one portion
2. stirringThe reaction was stirred for another 9 h at RT
3. customquenched with sat. NaHCO3
4. extractionThe aqueous mixture was extracted with EtOAc (40 mL
5. washwashed with brine (30 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customthese were removed
10. dissolutionby dissolving the mixture in a minimal volume of EtOAc
11. filtrationfiltering
12. concentrationSubsequent concentration