Pyridine → cis-2-(3-Methylbutylamino)-cyclopentanecarboxylic acid ethyl ester

Participants

Reaction Steps

To a solution of 2-(3-methylbutylamino)-cyclopent-1-enecarboxylic acid ethyl ester (6.84 g, 30.4 mmol) in acetic acid (100 mL) was added a 8.0 M solution of borane in pyridine (4.6 mL, 36.8 mmol) at 25° C. After stirring for 15 min, the reaction mixture was concentrated in vacuo. The crude material was triturated with 1.0 M aqueous hydrochloric acid solution (25 mL) and stirred for 0.5 h (until the gas evolution ceased). The mixture was extracted with ethyl acetate (3×50 mL) and the combined organic layers were dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude material was purified by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-10% methanol in dichloromethane) to afford cis-2-(3-methylbutylamino)-cyclopentanecarboxylic acid ethyl ester (2.37 g, 10.4 mmol, 34%) as a colorless oil and trans-2-(3-methylbutylamino)-cyclopentanecarboxylic acid ethyl ester (1.18 g, 5.2 mmol, 17%) as a white solid. cis-2-(3-Methylbutylamino)-cyclopentanecarboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3) δ 0.90 (6H, d, J=6.3 Hz), 1.26 (3H, t, J=7.0 Hz), 1.34-1.46 (3H, m), 1.57-1.74 (4H, m), 1.81-1.90 (1H, m), 1.94-2.04 (2H, m), 2.53 (1H, q, J=8.1 Hz), 2.59 (2H, t, J=7.5 Hz), 3.27 (1H, q, J=7.6 Hz), 4.11-4.17 (2H, m). trans-2-(3-Methylbutylamino)-cyclopentanecarboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3) δ: 0.92 (6H, d, J=6.8 Hz), 1.28 (3H, t, J=7.3 Hz), 1.41-1.47 (2H, m), 1.51-1.90 (5H, m), 2.00-2.09 (3H, m), 2.62-2.74 (3H, m), 3.38 (1H, q, J=7.2 Hz), 4.16 (2H, q, J=7.0 Hz). LC-MS (ESI) calcd for C13H25NO2 227.19, found 228.3 [M+H+].

Provenance & Evidence