Diazomethane → Ethyl 2-(3,5-difluoro-4-hydroxyphenyl)cyclopropanecarboxylate

Temperature

0 °C

Into a 100-mL round-bottom flask, was placed a solution of 3-methyl-1-nitro-3-nitrosoguanidine (1.25 g, 8.50 mmol, 6.80 equiv) in ether (19 mL). This was followed by the addition of a solution of potassium hydroxide (1.57 g, 27.98 mmol, 22.40 equiv) in water (2.5 mL) dropwise with stirring at 0° C. the mixture were stirred at 0 degree for 2 min, the diazomethane was made. The ether phase was separated and dried over anhydrous sodium sulfate. Then it was used for the reaction directly. 100-mL round-bottom flask, was placed ethyl (2E)-3-(3,5-difluoro-4-hydroxyphenyl)prop-2-enoate (285 mg, 1.25 mmol, 1.00 equiv), Pd(OAc)2 (47 mg, 0.21 mmol, 0.17 equiv), ether (12 mL). The mixture was cooled to 0 degree C., the ether solution of diazomethane which got above was added dropwise with stirring at 0° C. The resulting solution was stirred overnight at 0° C. in a water/ice bath. The reaction was then quenched by the addition of acetic acid. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (30/70). The collected fractions were combined and concentrated under vacuum. This resulted in 130 mg (39%) of ethyl 2-(3,5-difluoro-4-hydroxyphenyl)cyclopropane-1-carboxylate as colorless oil. Mass spectrum (ESI, m/z): Calcd. for C12H12F2O3, 243.1 (M+H). found 243.1

1. customInto a 100-mL round-bottom flask, was placed
2. stirringwere stirred at 0 degree for 2 min
3. customThe ether phase was separated
4. dry with materialdried over anhydrous sodium sulfate
5. customThen it was used for the reaction directly
6. custom100-mL round-bottom flask, was placed
7. temperatureThe mixture was cooled to 0 degree C
8. additionabove was added dropwise
9. stirringwith stirring at 0° C
10. stirringThe resulting solution was stirred overnight at 0° C. in a water/ice bath
11. customThe reaction was then quenched by the addition of acetic acid
12. concentrationThe resulting mixture was concentrated under vacuum
13. concentrationconcentrated under vacuum
14. customThis resulted in 130 mg (39%) of ethyl 2-(3,5-difluoro-4-hydroxyphenyl)cyclopropane-1-carboxylate as colorless oil

ORD record

ord-f38f999dce014ef3af50b59e3461501d

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067898B1