5-Bromo-2-chloroanisole → HCID 20071127, compound

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Reaction Steps

Charge an oven dried, argon flushed 3-L 3-necked round bottomed flask equipped with a mechanical stirrer and reflux condenser with 2-acetoxy-3,4-dihydronaphthalene (100.69 grams, 0.5349 moles), 4-bromo-2-methoxy-1-chlorobenzene (116.81 grams, 0.5274 moles), palladium acetate (1.19 grams, 0.0053 moles), tri (ο-tolyl)phosphine (3.24 grams, 0.0107 moles), tri-n-butyltin methoxide (172.83 grams, 0.5383 moles) and 1 L toluene. Place in an oil bath pre-heated to 100°-105° C. for 20 hours. Distill off about 750 mL toluene, cool to RT, add 500 mL 5% HCl and 250 mL ethyl acetate, stir for a few minutes, filter through a pad of celite and wash the celite pad with 5×250 mL ethyl acetate. Separate the layers, extract the aqueous layer with 1×250 mL ethyl acetate, wash the combined organic layers with saturated sodium bicarbonate solution followed by saturated salt solution, dry over magnesium sulfate and concentrate on a Buchi rotavapor. Kugelrohr treat the resulting oil (heated to about 130° C., 1 Torr) to remove the more volatile by-products to yield product. An analytical sample can be prepared by flash chromatography (5-30% ethyl acetate/hexanes) followed by recrystallization (ethyl acetate/hexanes).

Provenance & Evidence