Triethylamine → 5-Difluoromethyl-pyridine-2-carboxylic acid methyl ester

A mixture of 2-bromo-5-difluoromethyl-pyridine (1.8 g, 8.9 mmol) [Lemoine, R. C. et al., Bioorg. Med. Chem. Lett. (2010), 20(16), 4753-56], palladium(II)acetate (19.9 g, 0.089 mmol), triethylamine (9.4 ml, 66.7 mmol) and 1,3-bis(diphenyphosphino)propane (361 mg, 0.89 mmol) in a 2:1-mixture of dry methanol and dimethylsulfoxide (32.5 ml) was heated at 60° C. in an autoclave at 600 psi of carbonmonoxide pressure. After heating for 24 hours, the reaction mixture was cooled and the solid was filtered off. The filtrate was concentrated at reduced pressure to afford the crude product. Ethyl acetate (60 ml) was added and the solution washed successively with water (3×15 ml) to remove the dimethylsulfoxide. After drying over sodium sulphate and concentration at reduced pressure the crude material (5.0 g) was purified by column chromatography using a 1:4-mixture of ethyl acetate and hexane as the eluent. The 5-difluoromethyl-pyridine-2-carboxylic acid methyl ester was obtained as a light yellow oil (1 g, 63% of theory).

1. temperatureAfter heating for 24 hours
2. temperaturethe reaction mixture was cooled
3. filtrationthe solid was filtered off
4. concentrationThe filtrate was concentrated at reduced pressure
5. customto afford the crude product
6. washthe solution washed successively with water (3×15 ml)
7. customto remove the dimethylsulfoxide
8. dry with materialAfter drying over sodium sulphate and concentration at reduced pressure the crude material (5.0 g)
9. customwas purified by column chromatography

ORDレコード

ord-9d3100ec3504440aa356aebd3d03fd5e

出典データセット

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08673894B2