Methanol → methyl N-[5-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-4-yl]carbamate

A mixture of 5-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-4-carboxylic acid (i.e. the product of Step D) (10.14 g, 37.8 mmol), diphenyl phosphoryl azide (8.15 mL, 10.4 g, 37.8 mmol) and triethylamine (6.32 mL, 4.59 g, 45.4 mmol) in toluene (100 mL) was stirred at room temperature for 2 h. After 2 h, the reaction mixture was added dropwise to toluene (100 mL) and heated at reflux for 2 h. The reaction mixture was cooled to about 70° C., methanol (30 mL) was added dropwise, and the mixture was again heated at reflux for an additional 40 minutes. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×40 mL) and the combined extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to provide the title compound as a light yellow solid (9.77 g).

1. waitAfter 2 h
2. temperatureheated
3. temperatureat reflux for 2 h
4. temperatureThe reaction mixture was cooled to about 70° C.
5. temperaturethe mixture was again heated
6. temperatureat reflux for an additional 40 minutes
7. extractionextracted with ethyl acetate (2×40 mL)
8. washthe combined extracts were washed with saturated aqueous sodium chloride solution
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-fada9468bbd0437c9f56d271ab3b274f

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09131693B2