反应详情

温度

0 °C

To a solution of 4-chloro-3-methylbenzoic acid (8.31 g, 48.7 mmol) in CH2Cl2 (50 mL) was added DMF (175 μm) and thionyl chloride (35.5 mL, 487 mmol) and the resulting mixture was refluxed for 1 hour. After cooling down, the mixture was evaporated to dryness and taken up in THF (50 mL). The resulting solution was cooled to 0° C. and triethylamine (13.5 mL, 97 mmol) was added followed by N,O-dimethylhydroxyl-amine hydrochloride (5.7 g, 58.4 mmol) and the resulting mixture was stirred at room temperature overnight. The mixture was diluted with CH2Cl2 and washed with 1 M KHSO4, saturated aqueous NaHCO3 and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The resulting crude Weinreb amide (10.4 g, 48.7 mmol) was taken up in THF (440 mL) and cooled to 0° C. under an argon atmosphere. Ethylmagnesium bromide (1 M in TBME, 97 ml, 97 mmol) was then slowly added and the resulting mixture was stirred for 2 hours at 0° C. The mixture was quenched with a saturated aqueous ammonium chloride solution. The THF was evaporated and the product was extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography on silica gel (cyclohexane/EtOAc) to give INT 5.

1. temperaturethe resulting mixture was refluxed for 1 hour
2. temperatureAfter cooling down
3. customthe mixture was evaporated to dryness
4. washwashed with 1 M KHSO4, saturated aqueous NaHCO3 and brine
5. dry with materialThe organic layer was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. temperaturecooled to 0° C. under an argon atmosphere
9. stirringthe resulting mixture was stirred for 2 hours at 0° C
10. customThe mixture was quenched with a saturated aqueous ammonium chloride solution
11. customThe THF was evaporated
12. extractionthe product was extracted with EtOAc
13. washThe organic layer was washed with brine
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. customThe residue was purified by chromatography on silica gel (cyclohexane/EtOAc)
18. customto give INT 5