4-Fluorobenzaldehyde → methyl (1R,2S)-2-(4-fluoro-benzylamino)-cyclopentanecarboxylate

Participants

Reaction Conditions

Reaction Steps

Methyl (1R,2S)-2-aminocyclopentanecarboxylate hydrochloride (4.32 g, 24.15 mmol) was dissolved in methanol (120 mL). Sodium acetate (3.96 g, 48.3 mmol) was added followed by 4 Å powdered molecular sieves (5.0 g) and 4-fluoro-benzaldehyde (2.55 mL, 24.15 mmol). Sodium cyanoborohydride (3.04 g, 48.3 mmol) was added and the mixture was stirred at 25° C. for 16 h. The mixture was poured into a mixture of saturated aqueous sodium bicarbonate solution (200 mL) and ethyl acetate (400 mL). After shaking, both layers were passed through a plug of Celite. The organic layer was further washed with saturated aqueous sodium bicarbonate solution (100 mL), saturated aqueous brine solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product, methyl (1R,2S)-2-(4-fluoro-benzylamino)-cyclopentanecarboxylate (5.38 g, 21.4 mmol, 89%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 1.55-1.72 (2H, m), 1.89 (3H, m), 2.05 (1H, m), 2.97 (1H, m), 3.32 (1H, m), 3.71 (3H, s), 3.77 (2H, m), 7.00 (2H, m), 7.28 (2H, m). LC-MS (ESI) calcd for C14H18FNO2 251.13, found 252.2 [M+H+].

Provenance & Evidence