反应详情

A mixture of phosphorous tribromide (18.95 g) and pyridine (3.76 cc) in 10 ml of benzene is chilled to -5° C. and treated with a solution of 2-(2-thienyl)-ethanol (25 g) in 10 ml of benzene containing 1.25 cc of pyridine at such a rate that the reaction temperature never exceeds 0° C. The mixture is then allowed to come to room temperature while stirring overnight. The reaction mixture is then concentrated on a water pump at 30°-40° C. to remove solvent and other volatiles, and the residue Claisen-distilled under water pump vacuum to yield 21 g of crude bromide (b.p. 115°-119° C.). This material is then fractionally distilled at 0.3 mm to provide 19 g of pure 2-(2-thienyl)-ethyl bromide (b.p. 50°-51° C.; 99.9% by gc). This bromide is dissolved in 40 ml of dry tetrahydrofuran and added, dropwise, to a stirred mixture of magnesium turnings (2.4 g) and 15 ml of dry tetrahydrofuran under nitrogen atmosphere. The mixture is then stirred and refluxed for 1 hour, cooled to room temperature, and added, dropwise under nitrogen, to a stirred mixture of diethyl oxalate (17.5 g) in 25 ml of dry tetrahydrofuran in a -15° C. bath. After completion the reaction mixture is stirred at -10° C. for 15 minutes, then allowed to warm to 10° C. and treated with 60 ml of saturated ammonium chloride solution. The aqueous layer is extracted twice with toluene; the combined organic layers dried over magnesium sulfate and concentrated in vacuo to provide 16.7 g of a mixture containing by gc analysis: solvent (26%); diethyl oxalate (10.5%); and ethyl 2-oxo-(2-thienyl)-butyrate (63.4%). The nmr spectrum (CDCl3) is consistent for this mixture, showing the presence of two specific types of ethyl esters, and the mass spectrum exhibits a peak at m/e=212 for the molecular ion of one keto-ester along with a fragmentation pattern consistent with structure.

1. additioncontaining by gc analysis