Reaction #7306

Reaction equation

cis-(4-methyl-piperidin-3-yl)-carbamic acid methyl ester

benzaldehyde

sodium triacetoxyborohydride

→

Cis-(1-Benzyl-4-methyl-piperidin-3-yl)-carbamic acid methyl ester

Yield 70.0%

Solvents

methylene chloride

Conditions

Workup

1. 1
   Otherto exotherm to 30°-35° C
2. 2
   OtherThe reaction was quenched with 78 ml saturated sodium bicarbonate (20 volumes)
3. 3
   Extractionextracted into 78 ml methylene chloride (20 volumes)
4. 4
   Concentrationconcentrated to a clear oil

Procedure

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).

Source