Toluene → (3,4-Dichloroisothiazol-5-yl)methanol

Temperature

100 °C

A mixture of 3,4-dichloroisothiazole-5-carboxylic acid (2.0 g) and toluene (20 mL) was treated with thionyl chloride (5.0 mL) and N,N-dimethylformamide (0.5 mL), and the resulting mixture was heated at 100° C. for 16 hours. The mixture was concentrated under reduced pressure and the residue was dissolved in tetrahydrofuran (5.0 mL). The mixture was cooled to −78° C. and treated dropwise over a period of 1 hour with a 2.0 M solution of sodium borohydride in N,N-dimethylformamide (8.5 mL). The mixture was stirred at −78° C. for 5 minutes, diluted with 1.0 M aqueous hydrochloric acid solution and extracted with ethyl acetate. The combined organic extract was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and dichloromethane (1:0 to 0:1 by volume) to afford the title compound as a pale yellow solid (1.1 g).

1. concentrationThe mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in tetrahydrofuran (5.0 mL)
3. temperatureThe mixture was cooled to −78° C.
4. additiontreated dropwise over a period of 1 hour with a 2.0 M solution of sodium borohydride in N,N-dimethylformamide (8.5 mL)
5. additiondiluted with 1.0 M aqueous hydrochloric acid solution
6. extractionextracted with ethyl acetate
7. extractionThe combined organic extract
8. washwas washed with saturated aqueous sodium chloride solution
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by column chromatography on silica gel
12. washeluting with a mixture of cyclohexane and dichloromethane (1:0 to 0:1 by volume)

ORD record

ord-e0db55158c1c439b802d8b5b3a1f3c86

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394836B2