4-Methylmorpholine → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of 1-(tert-Butoxycarbonyl)-4-piperidine carboxylic acid (2.29 g, 10 mmol) and 4-methyl morpholine (1.2 mL, 11 mmol) in THF (60 mL) cooled to −15° C. was added isobutyl chloroformate (1.36 mL, 10.5 mmol). To this solution was added N-methoxy-N-methyl amine (1.07 g, 11 mmol) in DMF (20 mL) followed by triethyl amine (1.53 mL, 11 mmol). The resulting reaction was warmed to room temperature. The reaction was quenched after 1 hour by adding a solution of saturated NaHCO3 (400 mL). The resulting mixture was extracted with EtOAc (3×). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude material was purified on the Biotage flash 40 M column using 1:1 ethyl acetate-hexanes as the solvent to give the title compound a colorless oil. 1H NMR (CDCl3, 500 MHz): δ 4.16 (bm, 2H), 3.73 (s, 3H), 3.21 (s, 3H), 2.79 (m, 3H), 1.7 (m, 4H), 1.48 (s, 9H). LC-MS: 1.75 min; (M-56)=217.

Provenance & Evidence