1,3-Difluorobenzene → tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate

HRID 1773683Notes

Reaction equation

HRID 1773683 reaction equation
[Li]CCCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1.[CH3:14][C:15]1[C:19]([C:20]2[CH:21]=[C:22]([CH:39]=[O:40])[C:23]3[N:27]=[C:26]([O:28][CH2:29][CH3:30])[N:25]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:24]=3[CH:38]=2)=[C:18]([CH3:41])[O:17][N:16]=1>C1COCC1>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[C:39]([C:22]1[C:23]2[N:27]=[C:26]([O:28][CH2:29][CH3:30])[N:25]([C:31]([O:33][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:32])[C:24]=2[CH:38]=[C:20]([C:19]2[C:15]([CH3:14])=[N:16][O:17][C:18]=2[CH3:41])[CH:21]=1)=[O:40]

Participants

5

Reactant 3

HCID 97411,3-DifluorobenzeneHCID 117601313tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-formyl-1H-benzo[d]imidazole-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 117601789tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-BuLi (0.58 mL, 0.93 mmol) was added dropwise to a solution of 1,3-difluorobenzene (0.102 mL, 0.1 mmol) in THF (5 mL) cooled to −78° C. and allowed to stir for 1 hour. tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-formyl-1H-benzo[d]imidazole-1-carboxylate (200 mg, 0.52 mmol) in THF was added and the reaction was allowed to stir for 5 mins at −78° C., quenched with ammonium chloride, extracted with EtOAc and concentrated. The crude was then taken up in DCM (2 mL), Des-Martin periodinane (290 mg, 0.78 mmol) was added and the reaction was allowed to stir for 15 mins. The reaction was quenched with sat. Na2S2O3, extracted with EtOAc, concentrated and purified by silica gel chromatography to give tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate.

Workup

  1. stirringto stir for 5 mins at −78° C.
  2. customquenched with ammonium chloride
  3. extractionextracted with EtOAc
  4. concentrationconcentrated
  5. additionDes-Martin periodinane (290 mg, 0.78 mmol) was added
  6. stirringto stir for 15 mins
  7. customThe reaction was quenched with sat. Na2S2O3
  8. extractionextracted with EtOAc
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-b4b93425df404970b1120659a84e7342
Source dataset
uspto-grants-2016_02
Patent number
US09255089B2

Reaction notes

Loading…