3,3-Dimethylbutanal → cis-2-(3,3-Dimethylbutylamino)-cyclopentanecarboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

Sodium acetate (0.423 g, 5.16 mmol), powdered 4 Å molecular sieves (1.0 g), 3,3-dimethylbutyraldehyde (0.324 mL, 2.58 mmol) and sodium cyanoborohydride (0.324 mg, 5.16 mmol) were added sequentially to a solution of (1R,2S)-2-amino-cyclopentanecarboxylic acid ethyl ester hydrochloride (prepared as described in Example 28b, 0.500 g, 2.58 mmol) in methanol (13 mL) at 25° C. The reaction mixture was stirred at 25° C. for 3.5 h, and then was diluted with ethyl acetate (50 mL) and half-saturated aqueous sodium bicarbonate solution (100 mL). After stirring for 20 min at 25° C., the mixture was filtered through Celite and the filtrate was partitioned between half-saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (2×100 mL). The organic layers were washed with saturated aqueous brine solution (100 mL), dried over sodium sulfate, filtered, and were concentrated in vacuo. The residue was purified by flash column chromatography (Analogix SuperFlash Column; 0-40% ethyl acetate in hexanes) to afford the desired product, (1R,2S)-2-(3,3-dimethyl-butylamino)-cyclopentanecarboxylic acid ethyl ester (0.210 g, 0.87 mmol, 33%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.90 (s, 9H), 1.28 (t, 3H, J=7.1 Hz), 1.31-1.40 (m, 2H), 1.55-1.66 (m, 3H), 1.82-2.02 (m, 5H), 2.58 (septet, 2H, J=3.3 Hz), 2.94 (q, 1H, J=7.1 Hz), 3.27 (q, 1H, J=7.0 Hz), 4.14 (q, 2H, J=7.3 Hz). LC-MS (ESI) calcd for C14H27NO2 241.2, found 242.2 [M+H+].

Provenance & Evidence