3-Aminopyridine → 2,2-dimethyl-N-(pyridin-3-yl)propanamide

Temperature

0 °C

To a solution containing 50 g (531 mmol) of 3-aminopyridine and 139 mL (797 mmol) of N,N-diisopropylethylamine in 800 mL of dichloromethane at 0° C. was carefully added through an addition funnel 72 mL (584 mmol) of pivaloyl chloride. The reaction mixture was stirred at 0° C. for 30 min then concentrated in vacuo. To the residue was added 600 mL of ethyl acetate and the organic solution was washed sequentially with water, 0.5N aqueous sodium bicarbonate solution and saturated aqueous brine (300 mL each). The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. To the crude solid was added 150 mL of ethyl acetate. The mixture was stirred vigourously for 30 min, then 300 mL of hexane was added and the mixture was stirred for an additional 30 min. The resultant crystalline solid was filtered and washed with 400 mL of 10% ethyl acetate/hexane to give the title compound. 1H NMR (500 MHz, CDCl3): δ 8.57 (d, J=2.5 Hz, 1H), 8.36 (dd, J=4.8, 1.4 Hz, 1H), 8.21-8.19 (m, 1H), 7.47 (br s, 1H), 7.30-7.27 (m, 1H), 1.36 (s, 9H).

1. concentrationthen concentrated in vacuo
2. additionTo the residue was added 600 mL of ethyl acetate
3. washthe organic solution was washed sequentially with water, 0.5N aqueous sodium bicarbonate solution and saturated aqueous brine (300 mL each)
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. filtrationfiltered
6. customevaporated in vacuo
7. additionTo the crude solid was added 150 mL of ethyl acetate
8. stirringThe mixture was stirred vigourously for 30 min
9. addition300 mL of hexane was added
10. stirringthe mixture was stirred for an additional 30 min
11. filtrationThe resultant crystalline solid was filtered
12. washwashed with 400 mL of 10% ethyl acetate/hexane

ORD record

ord-b3591189269f4ceabbdd68c916d48023

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08017624B2