4-Fluorobenzaldehyde → cis-2-(4-Fluoro-benzylamino)-cycloheptanecarboxylic acid methyl ester

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Reaction Conditions

Reaction Steps

cis-2-Amino-cycloheptanecarboxylic acid methyl ester hydrochloride (0.8 g, 3.86 mmol) was suspended in methanol (20 mL). Sodium acetate (0.63 g, 7.7 mmol) was added followed by 4 Å powdered molecular sieves (0.8 g) followed by 4-fluoro-benzaldehyde (0.48 g, 3.86 mmol). Sodium cyanoborohydride (0.48 g, 7.7 mmol) was added and the mixture stirred at 25° C. for 16 h. The mixture was poured into a 1:1 mixture of saturated aqueous sodium bicarbonate solution (200 mL) and ethyl acetate (200 mL). After shaking, both layers were passed through a plug of Celite. The organic layer was further washed with saturated aqueous brine solution (50 mL), dried over magnesium sulfate and concentrated in vacuo to afford the crude product, cis-2-(4-fluoro-benzylamino)-cycloheptanecarboxylic acid methyl ester (0.56 g, 2 mmol, 52%), as a clear oil. LC-MS (ESI) calcd for C16H22FNO2 279.16, found 280.3 [M+H+].

Provenance & Evidence