Sodium Bicarbonate → 5-(4-Fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

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Reaction Conditions

Reaction Steps

Under argon, 0.60 g (1.70 mmol) of 5-(4-fluorophenyl)-7-isopropyl-4-oxo-3,4-dihydrospiro-[chromen-2,1′-cyclobutane]-6-carbaldehyde (Example 51A) is suspended in 15 ml of tetrahydrofuran and cooled to −70° C. 4.3 ml (2.13 mmol) of a freshly prepared 0.5 M solution of [4-(trifluoromethoxy)phenyl]magnesium bromide in tetrahydrofuran are added slowly. The mixture is stirred briefly at −78° C. and then warmed to 0° C. After 1 h, the mixture is hydrolyzed with sodium bicarbonate solution, diluted with water and extracted repeatedly with ethyl acetate. The combined organic phases are washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The crude product is purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 25:1→10:1). This gives 710 mg (81% of theory) of the title compound in a purity of 70%.

Provenance & Evidence