tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate → Tert-butyl 4-(4-methoxy-3-methylbenzoyl)piperidine-1-carboxylate

Participants

Reaction Steps

A 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 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. 40 mL of saturated aqueous NH4Cl was added slowly 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.) t 1.57 min. 1H NMR (400 MHz, CDCL3) δ 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, 2H).

Provenance & Evidence