Sodium Carbonate → Ethyl 1-(6-{2-[(2,4-dimethylbenzyl)oxy]-3-methylphenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1255192Notes

Reaction equation

HRID 1255192 reaction equation
[CH3:1][C:2]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:3]=1[CH2:4][O:5][C:6]1[C:11](I)=[CH:10][CH:9]=[CH:8][C:7]=1[C:13]1[N:18]=[C:17]([N:19]2[C:23]([C:24]([F:27])([F:26])[F:25])=[C:22]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:21]=[N:20]2)[CH:16]=[CH:15][CH:14]=1.[CH3:38]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1>[CH3:1][C:2]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:3]=1[CH2:4][O:5][C:6]1[C:11]([CH3:38])=[CH:10][CH:9]=[CH:8][C:7]=1[C:13]1[N:18]=[C:17]([N:19]2[C:23]([C:24]([F:27])([F:26])[F:25])=[C:22]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:21]=[N:20]2)[CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 574072TrimethylboroxineHCID 67159279Ethyl 1-(6-{2-[(2,4-dimethylbenzyl)oxy]-3-iodophenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 67159648Ethyl 1-(6-{2-[(2,4-dimethylbenzyl)oxy]-3-methylphenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A vial was charged with the product from Example 15 Step B (40 mg, 0.064 mmol), trimethyl boroxine (49 mg, 50 wt. %, 0.193 mmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (5.3 mg, 0.006 mmol). Sodium carbonate (0.161 mL, 1.0 M aqueous, 0.161 mmol) and THF (0.25 mL) were added, and the resulting suspension was degassed by a nitrogen sparge. The vial was then capped and placed in a pre-heated (65° C.) oil bath. After 18 h, the reaction mixture was allowed to cool to ambient temperature, then was poured into water. The aqueous phase was extracted with EtOAc, and the organic phase was concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 20% EtOAc in hexanes, then 20 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 510.8 [M+H]+.

Workup

  1. customthe resulting suspension was degassed by a nitrogen
  2. customsparge
  3. customThe vial was then capped
  4. temperatureto cool to ambient temperature
  5. additionwas poured into water
  6. extractionThe aqueous phase was extracted with EtOAc
  7. concentrationthe organic phase was concentrated in vacuo
  8. customPurification by flash chromatography on silica gel (0 to 20% EtOAc in hexanes

Sources & evidence

ORD record
ord-0f69f1c18ac444aabf2e6c64f41880bb
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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