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

Temperature

20 °C

The reductive amination of cis-(4-methyl-piperidin-3-yl)-carbamic acid methyl ester was carried out by charging 3.9 grams (1 equiv., 22.6 mmol) to 2.07 ml benzaldehyde (0.9 equiv., 20.4 mmol), 9.6 grams sodium triacetoxyborohydride (2 equivs., 45.3 mmol) and 39 ml methylene chloride (10 volumes). The reaction was stirred at 20° C. and was allowed to exotherm to 30°-35° C. The reaction was complete by GCMS within 30 minutes. The reaction was quenched with 78 ml saturated sodium bicarbonate (20 volumes), extracted into 78 ml methylene chloride (20 volumes) and concentrated to a clear oil. (70% yield). 1H NMR: δ7.2-7.3 (5 H, m, aromatic protons), 5.50-5.48 (1 H, d, J=8.8 Hz), 3.77-3.75 (1 H, d, J=8.0 Hz), 3.63 (3 H, s), 3.45-3.38 (2 H, m), 2.77-2.74 (2 H, d, J=11.2 Hz), 2.14-2.01 (1 H, m), 1.94-1.89 (1 H, m), 1.57-1.55 (1 H, brs), 1.37-1.20 (2 H, m), 0.876 (3 H, d, J=9.2 Hz).

1. customto exotherm to 30°-35° C
2. customThe reaction was quenched with 78 ml saturated sodium bicarbonate (20 volumes)
3. extractionextracted into 78 ml methylene chloride (20 volumes)
4. concentrationconcentrated to a clear oil

ORD record

ord-aa9d08d4a8be45e7b7b7d7d151edf62c

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07084277B2