Potassium Carbonate → (+)-2-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methylquinolin-7-yl)phenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(4-bromo-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide (0.223 mmol) in dry 1,4-dioxane (1.5 mL) was treated with bis(pinacolato)diboron (0.268 mmol), potassium acetate (0.499 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.011 mmol). The solution was degassed with nitrogen, sealed, and stirred at 100° C. for 3 hours. The reaction mixture was cooled to room temperature and was treated with 7-bromo-3-methylquinoline (0.223 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.011 mmol) and 2M aq potassium carbonate (0.669 mmol). The reaction vessel was purged with nitrogen gas, sealed, and irradiated in a Biotage Initiator Microwave at 120° C. for 15 minutes. The resulting black mixture was diluted with water (50 mL) and extracted with dichloromethane three times. The combined organic layer was treated with Silicycle Si-thiol (30 mg), dried over sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-10% methanol/dichloromethane followed by 30% methanol/dichloromethane) and resolution by chiral HPLC (Chromegachiral CC4, methanol) afforded the title compound in >99% ee (31% yield). MS(ES)+ m/e 503.2 [M+H]+. αD=+ 38 deg (c=0.03, methanol).

Provenance & Evidence