Benzyl Bromide → (E)-3-{1'-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-6-yl}-acrylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

(E)-3-{1′-Tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (1.8 g, 4.5 mmol, Example 25, Step A) was dissolved in dry DMF (25 ml) under N2, and NaH (268.6 mg, 6.71 mmol, 60% suspension in mineral oil) was added. After 10 min stirring, benzyl bromide (1.07 ml, 8.95 mmol) was added dropwise and the mixture was heated for 3 h at 80° C. The mixture was poured into water and a saturated NH4Cl solution was added. The aqueous phase was extracted with DCM, and the combined organic phases were dried and concentrated. The crude residue was purified by column chromatography (eluent: petroleum ether/AcOEt 90:10 to 70:30) to give (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (1.3 g, 59%) as a white solid.

Provenance & Evidence