Water → 5-Cyano-3-methylpyridine-2-carboxylic acid

Temperature

33 °C

To the stirred solution of 5-cyano-3-methylpyridine-2-carboxylic acid tert-butyl ester (20.7 g, 94.9 mmol) in toluene (200 mL) was added H2O (3.4 mL) at ambient temperature. The mixture was then cooled to 0˜5° C. with stirring, at this point, TFA (200 mL) was added to the mixture slowly while maintaining the reaction temperature at 25˜35° C. The reaction mixture was then heated at 33° C. with stirring. After 60 min, to the reaction mixture was added toluene and the mixture was concentrated in vacuo to ˜¼ of the original volume to remove TFA by azeotropic distillation with toluene. To the concentrated mixture was added toluene and the mixture was evaporated in vacuo to ˜¼ of the original volume. The same evaporation manipulation was repeated once and the precipitated product was collected by filtration. The filter cake was washed with toluene and dried in vacuum oven at 50° C. for 8 h to give the title compound as a pale yellow crystalline solid: ESIMS: 163; [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 8.90 (s, 1H), 8.35 (s, 1H), 2.46 (s, 3H).

1. temperatureThe mixture was then cooled to 0˜5° C.
2. additionwas added to the mixture slowly
3. temperaturewhile maintaining the reaction temperature at 25˜35° C
4. concentrationthe mixture was concentrated in vacuo
5. customto remove TFA
6. distillationby azeotropic distillation with toluene
7. additionTo the concentrated mixture was added toluene
8. customthe mixture was evaporated in vacuo
9. filtrationthe precipitated product was collected by filtration
10. washThe filter cake was washed with toluene
11. customdried in vacuum oven at 50° C. for 8 h

ORD record

ord-b6f086ae8b1046058d1d0ab92c97b64b

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08338413B1