Sodium Hydroxide → 4-({Cyclohexyl[2-ethyl-5-(1-hydroxy-2-methylpropyl)thiophen-3-yl]methyl}amino)benzoic acid

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Reaction Steps

To a solution of methyl 4-{[cyclohexyl(2-ethyl-5-formylthiophen-3-yl)methyl]amino}benzoate (540 mg) synthesized in Example 287 (6) in tetrahydrofuran (10 mL) was added dropwise 1.0M isopropylmagnesium bromide-tetrahydrofuran solution (3.50 mL) at −45° C., and the mixture was stirred for 3 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (25% ethyl acetate/hexane) to give a yellow oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (5 mL), and the mixture was stirred with heated under reflux for 5 hr, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (5 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title compound (350 mg, 60%) as a pale-yellow solid. The obtained resultant product was a mixture of two diastereomers (about 2:3).

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