Sodium Carbonate → 4-(4-Fluorophenyl)-7-methyl-2-quinolinecarbonitrile

Temperature

100 °C

4-Chloro-7-methylquinoline-2-carbonitrile (1-5, 2.47 g, 12.2 mmol, 1.0 equiv.), 4-fluorophenylboronic acid (2.05 g, 14.63 mmol, 1.2 equiv.), Pd(PPh3)4 (0.7 g, 0.61 mmol, 0.05 equiv), and 1M aqueous Na2CO3 (12.2 ml, 2.39 mmol) was added into 1,4-dioxane (40 mL). The mixture was degassed and stirred at 100° C. for 16 hours, until disappearance of the starting material. The mixture was cooled, saturated aqueous sodium hydrogen carbonate (2 mL) was added and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic fractions were washed with brine, dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was treated with 50 ml of MeOH, stirred vigorously at rt for 1 h, the mixture was filtered and washed with MeOH. The solid was collected and dried under vacuum. The filtrate was concentrated and retreated with MeOH to get a second crop of white solid that was combined to the first to give 2.75 g of 4-(4-fluorophenyl)-7-methylquinoline-2-carbonitrile (1-6). LRMS m/z (M+H)+ 263.3 found, 263.3 required.

1. customThe mixture was degassed
2. temperatureThe mixture was cooled
3. additionsaturated aqueous sodium hydrogen carbonate (2 mL) was added
4. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
5. washThe combined organic fractions were washed with brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customthe solvent was evaporated under reduced pressure
9. additionThe residue was treated with 50 ml of MeOH
10. stirringstirred vigorously at rt for 1 h
11. filtrationthe mixture was filtered
12. washwashed with MeOH
13. customThe solid was collected
14. customdried under vacuum
15. concentrationThe filtrate was concentrated
16. customto get a second crop of white solid

ORD record

ord-1fa4a12661894ea8a84d8cd447818399

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09278960B2