Hydrogen Bromide → 2-fluoro-N-(2-oxo-1H-pyridin-4-yl)-4-(trifluoromethyl)benzamide

HRID 1752969Notes

Reaction equation

HRID 1752969 reaction equation
[F:1][C:2]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([O:13]C)[CH:8]=1)=[O:5].Br>C(O)(=O)C>[F:1][C:2]1[CH:18]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=1)=[O:5]

Participants

4

Reactant 2

HCID 260Hydrogen Bromide2×HCID 867284622-fluoro-N-(2-methoxy-4-pyridyl)-4-(trifluoromethyl)benzamide

Product 1

HCID 867284632-fluoro-N-(2-oxo-1H-pyridin-4-yl)-4-(trifluoromethyl)benzamideYield 76.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To 2-fluoro-N-(2-methoxy-4-pyridyl)-4-(trifluoromethyl)benzamide (1.00 g, 3.18 mmol) in acetic acid (6.0 mL) was added HBr (33% in acetic acid) (3.9 mL of 33% w/v, 15.91 mmol) and the mixture stirred at 100° C. for 6 hours. Additional HBr (2 mL, 33% in acetic acid) was added and the mixture was stirred at room temperature overnight. The mixture was then heated at 100° C. for 2 hours before it was cooled to room temperature. The mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×). The combined organics were washed with water and brine (2×), dried over sodium sulfate, filtered and concentrated under reduced pressure. The solid was slurried in methyl-tert-butyl ether and filtered to give 2-fluoro-N-(2-oxo-1H-pyridin-4-yl)-4-(trifluoromethyl)benzamide (19) (731 mg, 76%). ESI-MS m/z calc. 301.05, found 301.3 (M+1)+; Retention time: 1.35 minutes (3 minute run). 1H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 10.70 (s, 1H), 7.96-7.85 (m, 2H), 7.75 (d, J=8.2 Hz, 1H), 7.35 (d, J=7.2 Hz, 1H), 6.81 (d, J=1.9 Hz, 1H), 6.41 (dd, J=7.2, 2.1 Hz, 1H) ppm.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. temperatureThe mixture was then heated at 100° C. for 2 hours before it
  3. temperaturewas cooled to room temperature
  4. customThe mixture was partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  7. washThe combined organics were washed with water and brine (2×)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. filtrationfiltered

Sources & evidence

ORD record
ord-b6a40f3bb4134da29484e356ac93dab3
Source dataset
uspto-grants-2015_10
Patent number
US09163042B2

Reaction notes

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