Cuminaldehyde → HCID 86612368, compound

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Reaction Steps

To a solution of tert-butyl (7-bromo-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-yl) carbamate (1.77 g, 4.78 mmol) obtained in Example 238 in THF (20 mL) was added dropwise at −78° C. under argon atmosphere n-butyllithium (1.60 M hexane solution, 6.25 mL, 10.0 mmol), and the mixture was stirred for 30 minutes. To the reaction solution was added dropwise at −78° C. a solution of 4-isopropylbenzaldehyde (815 mg, 5.50 mmol) in THF (5 mL). The reaction solution was warmed to room temperature and stirred for 1 hour. Water was added to the reaction solution and the product was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4) to obtain 1.20 g (yield: 59%) of tert-butyl (7-(hydroxy(4-isopropylphenyl)methyl)-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)carbamate. To a mixture of the compound (1.00 g, 2.27 mmol) in trifluoroacetic acid (5 mL) was added with ice-cooling triethylsilane (1.0 mL, 6.4 mmol), and the mixture was stirred at room temperature for 1 hour. After the reaction solution was concentrated under reduced pressure, to the residue was added an aqueous saturated sodium hydrogen carbonate solution and the aqueous layer was made alkaline, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product of 7-(4-isopropylbenzyl)-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-amine. To a solution of the compound (330 mg, about 1.02 mmol) and tert-butylacetyl chloride (0.16 mL, 1.12 mmol) in dichloromethane (30 mL) was added triethylamine (0.16 mL, 1.12 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution, the organic layer was separated, and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with 1 N hydrochloric acid and an aqueous saturated sodium hydrogen carbonate solution, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain 273 mg (yield: 17%) of the title compound. Melting point: 170-171° C. (ethyl acetate-hexane).

Provenance & Evidence