Acetic Acid → N-[(1S)-1-[4-[[4-(1,1-Dimethylethyl)-1-piperidinyl]methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide

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Reaction Steps

Charge a five liter round-bottom flask with DCM (1.5 L) and 4-tert-butylpiperidine hydrochloride (89 g, 0.5 mol). Add triethylamine (101.4 g, 1.0 mol) to the mixture at 21° C. followed by N-[(1S)-2,2,2-trifluoro-1-(4-formylphenyl)ethyl]methanesulfonamide (155 g, 0.55 mol), and acetic acid (36 g, 0.6 mol). Add sodium triacetoxyborohydride (318.6 g, 1.5 mol) portion-wise and stir the suspension at 22° C. for 15 hours. Add saturated aqueous solution of sodium bicarbonate (1800 mL) slowly with stirring until pH of the mixture is 8. Separate the organic layer and extract the aqueous layer with DCM (3×2000 mL). Dry the combined organic layers over MgSO4; filter; collect the filtrate; and concentrate the filtrate under vacuum. Purify the residue on silica gel column chromatography eluting with DCM:MeOH (100 to 95%) to provide the title compound as an off-white solid (126 g, 61.9%). MS (m/z): 407 (M+1).

Provenance & Evidence