Methyl Acrylate → (E)-3-{1'-benzyl-4-hydroxy-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester

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Reaction Steps

1′-Benzyl-6-bromo-4-hydroxy-spiro[chromane-2,4′-piperidine] (3.0 g, 7.7 mmol, Intermediate 3) was treated with methyl acrylate according to the procedure for preparation of Intermediate 1, Step B, giving (E)-3-{1′-benzyl-4-hydroxy-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (3.1 g). The crude intermediate was dissolved in THF (20 ml) under N2 and p-TsOH (0.15 g, 0.79 mmol) was added. The mixture was heated to reflux. After 16 h, the mixture was poured into water and a 10% NaOH solution was added until reaching a neutral pH value. The solution was extracted with DCM, dried over Na2SO4, filtered and evaporated under vacuum. The crude mixture was purified by column chromatography using DCM/MeOH (90/10) and then hexane/AcOEt (70/30) as eluent to give (E)-3-{1′-benzyl-spiro[chromene-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (150 mg).

Provenance & Evidence