Triethylamine → (1S,2R)-2-(4-fluoro-benzylamino)-cyclopentanecarboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of (1S,2R)-2-amino-cyclopentanecarboxylic acid methyl ester hydrochloride (136 mg, 0.76 mmol) in tetrahydrofuran (10 mL) at 25° C. was added magnesium sulfate (200 mg), triethylamine (0.11 mL, 0.80 mmol), and 4-fluorobenzaldehyde (0.17 mL, 1.56 mmol) sequentially. The reaction was stirred at 25° C. for 16 h. The mixture was passed through a short pad of Celite and the filtrate was concentrated and dried in vacuo. The residue was re-dissolved in methanol (10 mL) at 25° C. To this solution was added slowly sodium borohydride (59 mg, 1.56 mmol). The mixture was stirred at 25° C. for 1 h. It was then poured into a saturated aqueous sodium bicarbonate solution (10 mL) and the mixture was extracted into ethyl acetate (20 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a clear oil. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0-15% ethyl acetate in hexanes) afforded the desired product, (1S,2R)-2-(4-fluoro-benzylamino)-cyclopentanecarboxylic acid methyl ester (116 mg, 0.46 mmol, 79%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 1.55-1.73 (2H, m), 1.83-1.93 (3H, m), 1.99-2.08 (1H, m), 2.97 (1H, dd, J1=14.4 Hz, J2=8.0 Hz), 3.31 (1H, dd, J1=14.4 Hz, J2=7.2 Hz), 3.70 (3H, s), 3.77 (2H, dd, J1=19.6 Hz, J2=12.0 Hz), 4.67 (1H, s), 6.96-7.06 (2H, m), 7.26-7.35 (2H, m). LC-MS (ESI) calcd for C14H18FNO2 251.30, found 252.1 [M+H+].

Provenance & Evidence