Hydrochloric Acid → 1-(2-Fluoro-4-hydroxyphenyl)-2-methylpropan-1-one

Temperature

0 °C

Under an argon atmosphere, dehydrated THF (5 mL; Manufactured by Kanto Chemical Co., Inc.) was added to 4-(tert-butyldimethylsilyloxy)-2-fluorobenzonitrile (14.02 g) that can be produced by the method described in Reference Example 1 or the like, and the mixture was cooled to 0° C. Subsequently, a 0.78 mol/L isopropylmagnesium bromide-THF solution (89 mL; manufactured by Kanto Chemical Co., Inc.) was added dropwise thereto. After completion of the dropwise addition, the reaction solution was stirred for 20 minutes while the temperature was raised to room temperature, copper bromide (140 mg; manufactured by Wako Pure Chemical Industries, Ltd.) was added thereto, and the reaction solution was stirred for 1.5 hours at 60° C. The reaction solution was cooled to 0° C., water (21.4 mL) and 5 mol/L hydrochloric acid (21.4 mL) were added thereto, and the reaction solution was stirred to 6 hours at 60° C. 5 mol/L hydrochloric acid (21 mL) was further added, and the reaction solution was stirred for 13 hours at 60° C. The reaction solution was cooled to room temperature, and was extracted three times with ethyl acetate. The organic layer was washed with water and brine, and was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and n-hexane was added to the residue. Precipitates were filtered, and thus the title compound (8.69 g) was obtained.

1. customcan be produced by the method
2. additionAfter completion of the dropwise addition
3. temperaturewas raised to room temperature
4. stirringthe reaction solution was stirred for 1.5 hours at 60° C
5. temperatureThe reaction solution was cooled to 0° C.
6. stirringthe reaction solution was stirred to 6 hours at 60° C
7. stirringthe reaction solution was stirred for 13 hours at 60° C
8. temperatureThe reaction solution was cooled to room temperature
9. extractionwas extracted three times with ethyl acetate
10. washThe organic layer was washed with water and brine
11. dry with materialwas dried over anhydrous sodium sulfate
12. customThe solvent was evaporated under reduced pressure, and n-hexane
13. additionwas added to the residue
14. customPrecipitates
15. filtrationwere filtered

ORD record

ord-358c510da14743f58de8dffedec839f9

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008506B2