Ammonium Chloride → Tert-butyl 4-(4-methoxy-3-methylbenzoyl)piperidine-1-carboxylate

Participants

Reaction Steps

A stirred solution of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (3.0 g, 11.02 mmol) in 30 mL THF was cooled to 0° C., then (4-methoxy-3-methylphenyl)magnesium bromide (6.21 g, 27.5 mmol) was added dropwise via a syringe under N2 and the reaction mixture was stirred at the same temperature for 1.5 h, then gradually warmed up to room temperature over 1 h when the reaction was judged complete by LCMS. To the reaction mixture was slowly added 40 mL of saturated aqueous NH4Cl then the aqueous solution was extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine, dried over Na2SO4 and the solvent was removed to yield the crude product. Purification by flash chromatography gave the title compound as a white solid (1.97 g, 5.62 mmol, 51% yield). MS (ESI) m/z 334.4 (M+H+); HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 35-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) retention time=1.57 min. 1H NMR (400 MHz, CDCL3) 8 ppm 1.48 (s, 9H) 1.62-1.91 (m, 4H) 2.27 (s, 3H) 2.78-3.02 (m, 2H) 3.27-3.46 (m, 1H) 3.91 (s, 3H) 4.12-4.27 (m, 2H) 6.87 (d, J=8.59 Hz, 1H) 7.77 (t, J=8.10 Hz, 2H).

Provenance & Evidence