Sodium triacetoxyborohydride → 1-(2-{4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]piperidin-1-yl}ethyl)-7-fluoroquinoxalin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-[2-(4-aminopiperidin-1-yl)ethyl]-7-fluoroquinoxalin-2(1H)-one (Intermediate 140, 85 mg, 0.29 mmol), 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (WO 2004/058144) (49 mg, 0.29 mmol) and molecular sieves 3 Å in dry methanol/chloroform (1:1, 10 mL) was heated to 70° C. for 3 hours. The reaction was allowed to cool to room temperature and sodium triacetoxy borohydride (190 mg, 0.88 mmol) was added. After 30 minutes, the reaction was filtered through celite, the filtrate was concentrated to dryness, taken up in 15% methanol/chloroform, and washed with saturated sodium bicarbonate solution. The aqueous phase was reextracted twice with 15% methanol/chloroform. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness. Chromatography on silica gel with 5% methanol in dichloromethane containing 0.25% ammonium hydroxide gave 70 mg (54%) of the title compound as an off-white solid.

Provenance & Evidence