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

Temperature

25 °C

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+].

1. stirringAfter shaking
2. washThe organic layer was further washed with saturated aqueous sodium bicarbonate solution (100 mL), saturated aqueous brine solution (100 mL)
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo

ORD record

ord-035ff23a79364880b73a862ba57f0083

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582626B2