Benzaldehyde → Methyl ((3S,4S)-1-benzyl-4-methylpiperidin-3-yl)carbamate

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Reaction Steps

A mixture of racemic cis (4-methyl-piperidin-3-yl)-carbamic acid methyl ester hydrochloride (7.35 mmol), benzaldehyde (818 μL, 8.09 mmol), diisopropylethylamine (3.9 mL, 22.1 mmol) and 4 Å molecular sieves (7 g) in DCE (50 mL) was stirred at ambient temperature for 5 hours before the addition of sodium triacetoxyborohydride (2.34 g, 11.03 mmol). The resulting mixture was stirred for 60 hours then filtered through Celite® and the filtrate concentrated under vacuum. The resulting residue was purified by Isolute® SCX-2 (gradient: DCM to 2M NH3 in methanol solution) then column chromatography on silica gel (gradient: 0 to 5% 2M NH3 in methanol solution in DCM) to afford 1.56 g (81%) of racemic cis (1-benzyl-4-methyl-piperidin-3-yl)-carbamic acid methyl ester as a clear oil. LCMS (Method H, ESI): RT=1.53 and 0.35 min, m+H=263.9; 1H NMR (400 MHz, CDCl3) δ: 7.31-7.23 (m, 5H), 5.42 (d, 1H), 3.78 (d, 1H), 3.66 (s, 3H), 3.45 (s, 2H), 2.80-2.77 (m, 2H), 2.20-2.12 (m, 1H), 1.94 (td, 1H), 1.72-1.48 (m, 1H), 1.38 (m, 2H), 0.90 (d, 3H).

Provenance & Evidence