Hydrochloric Acid → HCID 58293743, compound

Participants

Reaction Steps

To a solution of EtMgBr (300 mL of 1.0M, 300 mmol) in THF (400 mL) at RT was added 2-bromo-3-methylthiophene (48.28 g, 272.7 mmol) dropwise. The mixture was stirred at RT for 72 hours. To the reaction mixture was added a solution of tert-butyl 4-oxopiperidine-1-carboxylate (54.33 g, 272.7 mmol) in THF at RT. The reaction was stirred for 3 hours and 2 N HCl was added to quench the reaction. The mixture was extracted with EtOAc and the combined organics washed with water, satd' NaHCO3 solution, and dried over MgSO4. Removal of the volatiles in vacuo gave a gummy product, to which was added EtOAc. After shaking for 10 min a white precipitate appeared, which was collected by filtration and washed with EtOAc. The filtrate was evaporated again and the precipitation step repeated to obtain additional product, which was combined with the solid previously collected to yield tert-Butyl 4-hydroxy-4-(3-methylthiophen-2-yl)piperidine-1-carboxylate (Compound 1052, 58 g, 71.5% yield; 1H NMR (300 MHz, DMSO-d6): δ 7.17 (d, J=5.0 Hz, 1H), 6.79 (d, J=5.1 Hz, 1H), 5.47 (s, 1H), 3.82 (brd, 2H), 3.09 (brs, 2H), 2.26 (s, 3H), 1.84-1.79 (m, 4H) and 1.41 (s, 9H).

Provenance & Evidence