Potassium bisulfate → (trans)-N-[[2-(3-methoxyphenyl)cyclopropyl]methyl]butanamide

Participants

Reaction Conditions

Reaction Steps

(trans)-2-(3-Methoxyphenyl)cyclopropanecarboxaldehyde: To a rapidly stirred suspension of LiAlH4 (7.74 g, 204 mmol) in THF (800 mL) at -45° C. was added a solution of the (trans)-N-methoxy-N-methyl-2-(3-methoxyphenyl)cyclopropanecarboxamide (40 g, 171 mmol) in THF (100 mL) maintaining the temperature below -40° C. by dropwise addition. After addition the cooling bath was removed and the reaction was allowed to warm to 5° C., then immediately recooled to -45° C. Potassium hydrogen sulfate (40 g, 300 mmol) in H2O (120 mL) was cautiously added dropwise, the temperature maintained below -30° C. throughout. After addition the cooling bath was removed and the suspension was stirred at room temperature for 30 min. The mixture was filtered through celite and the filter cake was washed with ether. The combined filtrates were then washed with cold 1N HCl, 5% K2CO3, brine, and dried over MgSO4. Concentration by rotary evaporation yielded the title compound as a clear oil (29.9 g, 99%): 1H NMR (300 MHz, CDCl3) δ1.49-1.58 (m, 1H), 1.65-1.73 (m, 1H), 2.10-2.19 (m, 1H), 2.58-2.67 (m, 1H), 3.80 (s, 3H), 6.66-6.78 (m, 3H), 7.21 (t, J=66 Hz, 1H), 9.32 (d, J=2.0 Hz, 1H).

Provenance & Evidence