Dimethylformamide → HCID 59807520, compound

HRID 912560Notes

Reaction equation

HRID 912560 reaction equation
P(Cl)(Cl)(Cl)=O.[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:17]([CH3:18])=[CH:16][CH:15]=[C:14]2[CH3:19])=[C:9]([C:20]([F:23])([F:22])[F:21])[CH:8]=1.CN([CH:27]=[O:28])C>>[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:17]([CH3:18])=[CH:16][C:15]([CH:27]=[O:28])=[C:14]2[CH3:19])=[C:9]([C:20]([F:23])([F:21])[F:22])[CH:8]=1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 67253060HCID 67253060, compound

Product 1

HCID 59807520HCID 59807520, compoundYield 37%

Conditions

Temperature
0 °C

Procedure

To anhyd DMF (10 mL) cooled under nitrogen to 0° C. was added phosphorous oxychloride (1.2 mL, 13.1 mmol). The resulting mixture was stirred at 0° C. for 30 min and then a solution of 1-[4-fluoro-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole (3.19 g, 12.4 mmol) in anhyd DMF (15 mL) was added portionwise. The reaction mixture was maintained at 0-3° C. for 10 min and then the reaction flask was heated on an oil bath at 95-100° C. After heating 1.5 h, the reaction mixture was cooled and poured onto 200 mL of ice cold 1 M NaOH. The resulting suspension was extracted twice with DCM. The combined extracts were dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (SiO2), eluting with EtOAc/Hex (10:90 to 30:70) to afford the title compound as a light yellow solid (1.3 g, 37%); 1H-NMR (CDCl3): δ 9.90 (s, 1H), 7.58 (dd, J=8, 3 Hz, 1H), 7.43 (m, 1H), 7.29 (dd, J=5, 8 Hz, 1H), 6.39 (s, 1H), 2.20 (s, 3H), 1.91 (s, 3H); MS (ESI) m/z 286 [M+H]+.

Workup

  1. temperatureThe reaction mixture was maintained at 0-3° C. for 10 min
  2. temperaturethe reaction flask was heated on an oil bath at 95-100° C
  3. temperatureAfter heating 1.5 h
  4. temperaturethe reaction mixture was cooled
  5. extractionThe resulting suspension was extracted twice with DCM
  6. dry with materialThe combined extracts were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (SiO2)
  9. washeluting with EtOAc/Hex (10:90 to 30:70)

Sources & evidence

ORD record
ord-812d6288ab3d4681935862ccf568cc85
Source dataset
uspto-grants-2011_09
Patent number
US08026237B2

Reaction notes

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