Hydrochloric Acid → HCID 89964783, compound

Participants

Reaction Conditions

Reaction Steps

To a microwave vial with 4-methoxy-N-(4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)benzamide (2 g, 4.67 mmol) was added HCl (5 M aqueous, 20 mL, 100 mmol). The vial was sealed and heated by microwave at 150° C. for 80 min. The reaction was then concentrated in vacuo and the residue dissolved in half saturated aqueous NaHCO3 (75 mL) and DCM (50 mL). The organic layer was separated, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated to give a green oil. Purification by ISCO (40 g SiO2, 10-100% acetone in hexanes) gave racemic title compound. 4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-amine ( ) was separated by preparative SFC (using a AD-H (2×15 cm); mobile phase: 12% isopropanol (DEA)/CO2, at a flow rate of 60 mL/min] resulting in Peak 1 and 2 fractions with enantiomeric excess >99%).

Provenance & Evidence