Sulfuric Acid → (S)-1-{(E,3S,3aS,7aR)-7-(bromomethylene)-octahydro-3a-methyl-1H-indene-3-yl}ethanol

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, a suspension of bromomethyltriphenylphosphonium bromide (319 mg, 0.7304 mmol) in toluene (0.4 ml) was cooled in an ice bath, and potassium hexamethyldisilazide (0.5 M in toluene, 1.3 ml, 0.6492 mmol) was added dropwise thereto. The reaction mixture was stirred at 0° C. for 1 hour and 20 minutes, and at room temperature for 8 minutes, and then heated to 42° C. A solution of (S)-1-{(3S,3aR,7aR)-octahydro-3a-methyl-7-oxo-1H-indene-3-yl}ethyl formate (Compound 17: 36.4 mg, 0.1623 mmol) in toluene (0.25 ml) was added thereto. The vessel of (S)-1-{(3S,3aR,7aR)-octahydro-3a-methyl-7-oxo-1H-indene-3-yl}ethyl formate (Compound 17) was washed with toluene (0.1 ml×2) and the washings were added. The reaction mixture was stirred at from 41° C. to 46° C., and then cooled in an ice bath. Saturated aqueous ammonium chloride solution (2 ml), water (5 ml) and methanol (1.5 ml) were added thereto, and the resulting mixture was extracted with hexane (25 ml). The organic layer was washed with saturated brine (5 ml), dried over sodium sulfate, and evaporated under reduced pressure. The obtained crude product (169.4 mg) was dissolved in dioxane (0.5 ml), and the resulting mixture was cooled in an ice bath. To the mixture, 50 v/v % sulfuric acid (0.5 ml) was added, and the reaction mixture was stirred at room temperature (22° C.) for 1.5 hours. After cooling the resulting mixture in an ice bath, the mixture was diluted with ether (10 ml). Potassium carbonate (0.56 g) and water (5 ml) were added thereto. After separating the organic layer, the aqueous layer was extracted twice with ether (10 ml). The combined organic layer was washed with saturated brine (5 ml), dried over sodium sulfate, and evaporated under reduced pressure. The obtained crude product was purified by flash column chromatography to obtain (S)-1-{(E,3S,3aS,7aR)-7-(bromomethylene)-octahydro-3a-methyl-1H-indene-3-yl}ethanol (20.6 mg, 46.5%).

Provenance & Evidence