Acetic Acid → (R)-N-(3-bromo-4-methoxybenzyl)-1-(3-fluorophenyl)ethanamine

Participants

Reaction Conditions

Reaction Steps

(R)-1-(3-Fluorophenyl)ethanamine 115 (1.24 g, 8.92 mmol) and 3-bromo-4-methoxybenzaldehyde 114 (1.92 g, 8.92 mmol) were mixed in 100 mL anhydrous methanol in a round bottom flask. After the mixture was stirred at 20° C. for 10 min, the flask was cooled in an ice-water bath. To this flask was added sodium cyanoborohydride (0.56 g, 8.92 mmol) followed by acetic acid (0.54 g, 8.92 mmol). The resulting mixture was stirred for 12 h and allowed to warm to 20° C. After removing most of the methanol, the remaining residue was dissolved in 200 mL ethyl ether and washed with saturated sodium bicarbonate, 3 times. The organic phase was dried over sodium sulfate. After removing the solvent under reduced pressure, the remaining residue was subjected to a silica gel column using 50% ethylacetate in hexane as the eluant to yield a colorless oil as the pure product (R)—N-(3-bromo-4-methoxybenzyl)-1-(3-fluorophenyl)ethanamine 116 (2.3 g, yield=93%). LCMS (M+1) 338, calc. for C16H17BrFNO 338; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.34 (d, J=6.26 Hz, 3H) 3.46-3.60 (m, 2H) 3.78 (q, J=6.39 Hz, 1H) 6.84 (d, J=8.22 Hz, 1H) 6.90-6.98 (m, 1H) 7.09 (t, J=9.00 Hz, 2H) 7.16 (dd, J=8.41, 2.15 Hz, 1H) 7.27-7.34 (m, 1H) 7.48 (d, J=1.96 Hz, 1H).

Provenance & Evidence