Hydrochloric Acid → (1R,2R)-2-(3,4-Difluorophenyl)cyclopropanecarboxylic acid

温度

82.5 °C

(1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarbonitrile (5 g), ethanol (25 mL) were charged to a round bottom flask followed by addition of caustic lye (10 mL). The reaction mixture was heated to 80-85° C. and maintained at the same temperature for 2-3 hours till the completion of reaction as monitored by TLC. The reaction mixture was cooled to 25-30° C. and then water (15 mL) was added to the mixture. The pH of the mixture was adjusted to 1-2 with conc. hydrochloric acid (15 mL) followed by addition of ethyl acetate (25 mL). The layers were separated and aqueous layer was extracted with ethyl acetate (25 mL). The organic layers were combined and charged with water (15 mL) and caustic lye (10 mL). After stirring, the organic layer was separated and pH of the aqueous layer was adjusted to 1-2 with conc. hydrochloric acid (10 mL). To this ethyl acetate (25 mL) and water (15 mL) were added and stirred for 10-15 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate (25 mL). The organic layers were combined and washed with water (2×15 mL) followed by complete distillation of solvent from organic layer under vacuum at 50-55° C. to afford the title compound in about 94.3% yield having HPLC purity of about 99%.

1. additionfollowed by addition of caustic lye (10 mL)
2. temperaturemaintained at the same temperature for 2-3 hours till the completion of reaction
3. temperatureThe reaction mixture was cooled to 25-30° C.
4. customThe layers were separated
5. extractionaqueous layer was extracted with ethyl acetate (25 mL)
6. additioncharged with water (15 mL) and caustic lye (10 mL)
7. customthe organic layer was separated
8. additionTo this ethyl acetate (25 mL) and water (15 mL) were added
9. stirringstirred for 10-15 minutes
10. customThe layers were separated
11. extractionthe aqueous layer was extracted with ethyl acetate (25 mL)
12. washwashed with water (2×15 mL)
13. distillationfollowed by complete distillation of solvent from organic layer under vacuum at 50-55° C.

ORDレコード

ord-b5768b51ef8e4476adc076e16c6f3b71

出典データセット

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09233966B2