Thionyl Chloride → HCID 67530166, compound

Participants

Reaction Conditions

Reaction Steps

The above mixture of ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)-methyl)-3-(1-bromo-cyclohexyl)-isoxazole-5-carboxylate and ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-(1-cyclohexenyl)-isoxazole-5-carboxylate was dissolved in 40 mL of THF and cooled to −78° C. Potassium tert-butoxide solution (6.9 mL, 6.9 mmol, 1M in THF) was added dropwise, and the mixture was stirred for 14 hours, the cold bath allowed to evaporate spontaneously. The reaction mixture was cooled in an ice bath and quenched with 20 mL of 1M HCl. The product was extracted with EtOAc and the organic layer was dried over MgSO4 and concentrated to give 0.8 g of crude oil. The crude intermediate was dissolved in 12 mL of CH2Cl2. Thionyl chloride (0.2 mL, 2.73 mmol) was added and the reaction mixture was stirred for 5 h at ambient temperature. The volatiles were evaporated and the residue was partitioned between CH2Cl2 (50 mL) and saturated sodium bicarbonate solution (50 mL). To the vigorously stirring biphasic mixture was added 4M hydrochloric acid until pH was 2. The aqueous layer was extracted with additional CH2Cl2 and the combined organic layer was dried over MgSO4 and concentrated. The crude residue was purified by chromatography (0-100% CH2Cl2/hexanes) to give 210 mg of the title compound. MS: (+) m/z 289.30 (M+1).

Provenance & Evidence