Triphenylphosphine → 7-methoxy-5-(N-methylpiperidin-4-yloxy)-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-one

Participants

Reaction Steps

(5-hydroxy-7-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate (500 mg, 1.63 mmol), 4-hydroxy-N-methylpiperidine (280 mg, 2.45 mmol) and triphenylphosphine (640 mg, 2.45 mmol) were dissolved in anhydrous dichloromethane (8 ml), under a nitrogen atmosphere at 0° C. A solution of di-tert-butyl azodicarboxylate (560 mg, 2.45 mmol) in dichloromethane (1 ml) was added dropwise over 5 minutes and the resulting yellow solution was allowed to warm to ambient temperature and stirred for 18 hours. A further 1 equivalent of all reagents was added in the same sequence as above under the same reaction conditions and was left to stir for a further 12 hours at ambient temperature. The reaction mixture was concentrated in vacuo and the residue purified by chromatography on silica gel, eluting with 2-8% methanol in dichloromethane, to yield (7-methoxy-5-((1-methylpiperidin 4-yl)oxy)-4-oxoquinazolin-3(4H)-yl)methyl pivalate (370 mg, 56% yield) as a cream solid:

Provenance & Evidence