Ammonium Hydroxide → 4-Amino-3-chloro-5,6-difluoropicolinonitrile

A solution of 3-chloro-4,5,6-trifluoropicolinonitrile (200 g) in EtOAc (3 L) was cooled to 10° C. To this was slowly added 14% aq NH4OH (1296 g) keeping the temperature between 18-23° C. The aqueous solution was separated from the organic solution. The organic phase was washed sequentially with a 50/50 solution of aqueous saturated NaCl and water (500 mL) and satd NaCl solution (250 mL). The organic phase was concentrated under vacuum at 50° C. to about 500 mL volume as the product crystallized out. To this slurry was added heptane (1 L), and the mixture was concentrated under vacuum. The solids were collected by filtration. This solid was washed with pentane and dried under vacuum to give 4-amino-3-chloro-5,6-difluoropicolinonitrile (173.8 g, 90%, 99.6% purity) as a white crystalline solid: mp 190-191.5° C.; 13CNMR (101 MHz, DMSO-d6) δ 150.03 (dd, J=232.4, 12.5 Hz, C6), 144.29 (dd, J=11.4, 6.9 Hz, C4), 133.72 (dd, J=257.9, 30.8 Hz, C5), 122.14 (dd, J=19.6, 4.9 Hz, C2), 119.31 (s, C3), 114.25 (s, CN); 19F NMR (376 MHz, DMSO-d6) δ −91.24 (d, J=24.2 Hz), −154.97 (d, J=24.2 Hz); ELMS m/z 189 (Mr). Anal. Calcd for C6H2ClF2N3: C, 38.02; H, 1.06; N, 22.17. Found: C. 37.91; H. 1.00; 22.02.

1. custombetween 18-23° C
2. customThe aqueous solution was separated from the organic solution
3. washThe organic phase was washed sequentially with a 50/50 solution of aqueous saturated NaCl and water (500 mL) and satd NaCl solution (250 mL)
4. concentrationThe organic phase was concentrated under vacuum at 50° C. to about 500 mL volume as the product
5. customcrystallized out
6. additionTo this slurry was added heptane (1 L)
7. concentrationthe mixture was concentrated under vacuum
8. filtrationThe solids were collected by filtration
9. washThis solid was washed with pentane
10. customdried under vacuum

ORD record

ord-f0a3399b708f475ebe30c5d6fb729d4a

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993772B2