Sodium Bicarbonate → 5-Cyclohex-1-en-1-yl-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one

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Reaction Steps

At −78° C., 2.03 ml (1.02 mmol) of a freshly prepared 0.5 M solution of bromo[4-(trifluoromethyl)phenyl]magnesium in tetrahydrofuran are slowly added dropwise to a solution of 255 mg (780 μmol) of 5-cyclohex-1-en-1-yl-7-isopropyl-2,2-dimethyl-4-oxochroman-6-carbaldehyde (Example 33A) in 6 ml of tetrahydrofuran. The mixture is then allowed to thaw slowly to −20° C. and stirred at this temperature for 45 min. A further 300 μl (193 μmol) of the above Grignard solution are added and stirring is continued for a further hour, the solution slowly thawing to 0° C. 10% strength sodium bicarbonate solution is then added, the mixture is extracted three times with ethyl acetate and the combined organic phases are washed with saturated sodium chloride solution. The organic phases are dried over magnesium sulfate and the solvent is then removed under reduced pressure. The residue is dissolved in a mixture of cyclohexane and ethyl:acetate (10:1), whereupon the target product crystallizes and is filtered off. The filtrate is concentrated and the residue is purified by column chromatography on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 20:1→10:1). The resulting target product is combined with the crystals. The compound is present in the form of atropisomers (1:1).

Provenance & Evidence