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

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).

1. customthe volatiles were removed
2. customthe residue was partitioned between 5% aqueous acetic acid and ethyl acetate
3. washThe combined organic extracts were washed with brine
4. filtrationThe extract was filtered
5. customthe volatiles were removed under vacuum
6. dissolutionThe residue was dissolved in methanol (60 mL)
7. temperaturecooled to 0° C. under argon atmosphere
8. stirringthe solution was stirred at room temperature
9. waitAfter 2-3 hours
10. customthe volatiles were removed
11. additiontoluene was added
12. customthe volatiles were removed again

ORD record

ord-42c5f7b3b8b64d0981a36140ec4669aa

Source dataset

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06849657B2