3,3-Dimethylbutanal → cis-2-(3,3-Dimethyl-butylamino)-cycloheptanecarboxylic acid methyl ester

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Reaction Conditions

Reaction Steps

Sodium acetate (0.197 g, 2.40 mmol), powdered 4 Å molecular sieves (0.60 g), 3,3-dimethylbutyraldehyde (0.151 mL, 1.20 mmol) and sodium cyanoborohydride (0.151 mg, 2.40 mmol) were added sequentially to a solution of cis-2-amino-cycloheptanecarboxylic acid methyl ester hydrochloride (prepared as described in Example 2a, 0.250 g, 1.20 mmol) in methanol (10 mL) at 25° C. The reaction mixture was stirred at 25° C. for 3 h, and then was partitioned between half-saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (2×150 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; 0-25% ethyl acetate in hexanes) to afford the desired product, cis-2-(3,3-dimethyl-butylamino)-cycloheptanecarboxylic acid methyl ester (0.090 g, 0.352 mmol, 29%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.90 (s, 9H), 1.33-1.37 (m, 2H), 1.43-1.50 (m, 3H), 1.58-1.87 (m, 7H), 2.46-2.53 (m, 1H), 2.58-2.65 (m, 1H), 2.81-2.85 (m, 1H), 2.95-2.99 (m, 1H), 3.67 (s, 3H). LC-MS (ESI) calcd for C15H29NO2 255.22, found 256.3 [M+H+].

Provenance & Evidence