Sodium hydride → [2-(3-Methoxyphenyl)-3,4-dihydro-6-methoxynaphthalen-1-yl][4-methoxyphenyl]methanone

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Reaction Conditions

Reaction Steps

Sodium hydride (60% in mineral oil, 5.4 g, 0.135 mol) was suspended in anhydrous THF (80 mL) under a nitrogen atmosphere and the mixture was cooled to 5° C. in an ice bath. A solution containing 3,4-dihydro-6-methoxy-1-(4-methoxybenzoyl)-2(1H)-naphthalenone (38.0 g, 0.122 mol) and diphenyl chlorophosphate (36.3 g, 28.0 mL, 0.135 mol) in THF (150 mL) was added at a rate so that the temperature of the reaction mixture remained below 10° C. Following the initially rapid evolution of hydrogen gas, the reaction mixture was stirred for 2 hr with continued cooling from the ice bath. Analysis of a small sample by TLC (SiO2, Toluene:EtOAc, 9:1) showed essentially quantitative formation of the enolphosphate intermediate. The reaction mixture was maintained near 0° C. and 3-methoxyphenyl magnesium bromide (250 mL of a 0.74 M solution in THF, 0.185 mol) was added by cannula over approximately 5 min. The resulting mixture was stirred at 0° C. for 2 hour, and then it was allowed to warm to 25° C. overnight. By TLC analysis, loss of enolphosphate had accompanied the formation of a major product, which migrated at high Rf. The reaction was worked up by pouring it over a large excess of iced NH4Cl solution, and the crude product was extracted with ethyl acetate. The organic extracts were washed with brine and dried over anhydrous sodium sulfate. After filtration and removal of the solvents, a brown oil was obtained. The oil was purified by chromatography over silica gel, which employed a hexane to chloroform gradient. Pooling and concentration of appropriate fractions gave an amber oil which amounted to 40.3 g (83%). 1H NMR (CDCl3) δ 7.85 (d, J=8.6 Hz, 2H)7.10-7.0 (m, 1H), 6.90-6.70 (m, 6H), 6.70-6.60 (m, 2H), 3.80 (s, 6H), 3.67 (s, 3H), 3.10-2.90 (m, 2H), 2.90-2.70 (m, 2H); MS (FD) m/e 400 (M+); Anal. Calc'd. for C26H24O4 : C, 77.98; H, 6.04; N, 0.00. Found: C, 77.49; H, 6.20; N, 0.00.

Provenance & Evidence