反应详情

A mixture of 1.0 g. of 2,3-dimethylbutyric acid (8.6 mmol.) and 2.5 ml. of thionyl chloride (34.3 mmol.) in 10 ml. of cyclohexane was refluxed on a steam bath for 1.5 hours. The resulting solution was then concentrated under reduced pressure and the residue azeotroped with cyclohexane to yield a colorless oil. The oil was then added dropwise to a cold, stirred suspension containing 0.8 g. of 7-chloro-4-(4-chlorophenyl)-2-(hydroxymethyl)-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one (2.0 mmol.) in 15 ml. of pyridine. After stirring for 35 minutes, the mixture was poured onto ice-water, resulting in the formation of a yellow precipitate which was filtered, washed with water and air-dried, then purified using flash chromatography on silica gel, employing a mixture of 5% ethyl acetate: 95% methylene chloride as the eluent. Fractions containing the product were combined and triturated with ether to yield 7-chloro-4-(4-chlorophenyl)-2-[(2,3-dimethyl-1-oxobutoxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one as a yellow crystalline solid (110 mg; 11% yield) having the structural formula, ##STR20## a melting point in the range of 204°-205° C. and the following elemental analysis:

1. additionA mixture of 1.0 g
2. concentrationThe resulting solution was then concentrated under reduced pressure
3. customthe residue azeotroped with cyclohexane
4. customto yield a colorless oil
5. additionThe oil was then added dropwise to a cold
6. additioncontaining 0.8 g
7. stirringAfter stirring for 35 minutes
8. additionthe mixture was poured onto ice-water
9. customresulting in the formation of a yellow precipitate which
10. filtrationwas filtered
11. washwashed with water
12. customair-dried
13. custompurified
14. additiona mixture of 5% ethyl acetate
15. additionFractions containing the product
16. customtriturated with ether