Hydrochloric Acid → cis-2-(3-Methyl-butylamino)-cycloheptanecarboxylic acid methyl ester

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Reaction Conditions

Reaction Steps

Sodium acetate (0.328 g, 4.00 mmol), powdered 4 Å molecular sieves (1.0 g), isovaleraldehyde (0.216 mL, 2.00 mmol) and sodium cyanoborohydride (0.251 mg, 4.00 mmol) were added sequentially to a solution of cis-2-amino-cycloheptanecarboxylic acid methyl ester hydrochloride (prepared as described in Example 2a, 0.415 g, 2.00 mmol) in methanol (10 mL) at 25° C. The reaction mixture was stirred at 25° C. for 16 h, then was acidified to pH=2 by the addition of 1.0 M aqueous hydrochloric acid solution. After stirring for 5 min at 25° C., the mixture was partitioned between half-saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (3×50 mL). The organic layers were washed sequentially with half-saturated aqueous sodium bicarbonate solution (100 mL) and saturated aqueous brine solution (100 mL), then were 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, cis-2-(3-methyl-butylamino)-cycloheptanecarboxylic acid methyl ester (0.340 g, 1.41 mmol, 70%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.89 (d, 6H, J=6.5 Hz), 1.33 (q, 2H, J=7.3 Hz), 1.43-1.50 (m, 3H), 1.57-1.66 (m, 3H), 1.72-1.79 (m, 3H), 1.81-1.87 (m, 2H), 2.47-2.54 (m, 1H), 2.59-2.66 (m, 1H), 2.79-2.84 (m, 1H), 2.95-2.99 (m, 1H), 3.67 (s, 3H). LC-MS (ESI) calcd for C14H27NO2 241.20, found 242.4 [M+H+].

Provenance & Evidence