Isopropanol → Methyl 4-[(2-chloroethyl)thio]butanoate

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Reaction Steps

A 0° C. isopropanol (70 mL) solution of 4-mercaptobutyric acid (3.85 g, 20 mmol) was treated with sodium hydride in four portions (95%, 1.56 g total, 65 mmol) over 20 minutes and allowed to warm to room temperature. 1-Bromo-2-chloroethane (11 mL, 128 mmol) was added rapidly with the resulting suspension stirred vigorously for 2 days, then the volatiles were removed, and the residue was partitioned between 5% aqueous acetic acid and ethyl acetate. The combined organic extracts were washed with brine and stored over sodium sulfate. The extract was filtered and the volatiles were removed under vacuum. The residue was dissolved in methanol (60 mL) and cooled to 0° C. under argon atmosphere. Thionyl chloride (5 mL, 69 mmol) was added dropwise and the solution was stirred at room temperature. After 2-3 hours, the volatiles were removed, toluene was added, and the volatiles were removed again. Chromatography yielded (2.93 g, 14 mmol) of methyl 4-[(2-chloroethyl)thio]butanoate as a colorless oil: MS (NH3) m/z 199 (M+1+ with 37Cl), 197 (M+1+ with 35Cl).

Provenance & Evidence