Water → 4-Amino-2,3-difluoro-5-nitrobenzonitrile

HRID 1928570Notes

Reaction equation

[NH2:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][C:5]([C:6]([NH2:8])=O)=[C:4]([F:14])[C:3]=1[F:15].O=P(Cl)(Cl)Cl.O>C(#N)C>[NH2:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][C:5]([C:6]#[N:8])=[C:4]([F:14])[C:3]=1[F:15]

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred suspension of 4-amino-2,3-difluoro-5-nitrobenzamide (90 g, 0.416 mol) in acetonitrile (630 mL) was added POCl3 (96 mL, 1.04 mol) in one portion. The mixture was then heated to 70° C. and as the reaction proceeded the suspension become a brown solution. After 1.5 hours, HPLC analysis showed no remaining starting material. The reaction mixture was cooled to 30° C., then added to water (4.5 L) over 30 minutes while the temperature was held at 17-25° C. The resultant bright yellow slurry was stirred for 1 hour, filtered under vacuum, and the remaining solid was then dried in a vacuum oven at 50° C. to provide 4-amino-2,3-difluoro-5-nitrobenzonitrile as a yellow solid, (74.4 g, 90% yield). HPLC 95a %. 1H NMR (400 MHz, DMSO-d6) δ 8.30 (2H, br s, NH2), 8.53 (1H, apparent dd, J 1.8, 6.4, Ar—H). 19F NMR (376 MHz, DMSO-d6) δ −128, −152. 13C (100 MHz, DMSO-d6) δ 87.1 (C, d, J 15), 113.6 (C, d, J 4), 128.6 (CH, s), 128.8 (C, d, J 5), 139.3 (CF, dd, J 245, 14), 141.5 (C, dd, J 13, 5), 152.8 (CF, dd, J 259, 12). IR νmax/cm−1 3446, 3322, 2235, 1647, 1551, 1287, 1275. MS APCI (−) 198 (M−1) detected, APCI (+) 200 (M+1) detected.

Workup

temperatureThe reaction mixture was cooled to 30° C.
customwas held at 17-25° C
filtrationfiltered under vacuum
customthe remaining solid was then dried in a vacuum oven at 50° C.

Sources & evidence

ORD record: ord-4bc988c39fd54bb48428d95ad0ed1325
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08183385B2

Reaction notes

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