Cesium carbonate → Methyl 2-(4-(pyrrolidin-1-ylmethyl)-2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxylate

HRID 85188Notes

Reaction equation

HRID 85188 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][CH:15]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[C:10]=3[N:9]=2)=[C:4]([C:21]([F:24])([F:23])[F:22])[CH:3]=1.[B-](F)(F)(F)[CH2:26][N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1.[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>>[N:27]1([CH2:26][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[NH:12][C:11]4[CH:13]=[CH:14][CH:15]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[C:10]=4[N:9]=3)=[C:4]([C:21]([F:24])([F:23])[F:22])[CH:3]=2)[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 45588176Potassium trifluoro[(pyrrolidin-1-yl)methyl]borateHCID 67201064HCID 67201064, compound

Product 1

HCID 67201270Methyl 2-(4-(pyrrolidin-1-ylmethyl)-2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxylate

Conditions

Temperature
80 °C

Procedure

A sealed tube containing the mixture of methyl 2-(4-chloro-2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxylate (390 mg, 1.10 mmol), potassium 1-trifluoroboratom-ethylpyrrolidine (158; 212 mg, 1.11 mmol), Pd (OAc)2 (22 mg, 0.03 mmol), XPhos (31 mg, 0.06 mmol), and cesium carbonate (1.0 g, 3.3 mmol) was evacuated and filled with nitrogen twice. To the mixture was added THF/H2O (10:1, 4.4 mL). The suspension was heated at 80° C. overnight and cooled to room temperature. Water (2 mL) was added and the reaction was extracted with CH2Cl2 twice. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. Purification by silica gel chromatography (MeOH/CH2Cl2+1% Et3N) afforded methyl 2-(4-(pyrrolidin-1-ylmethyl)-2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxylate (structure not shown) as a yellow solid (544 mg).

Workup

  1. additionA sealed tube containing
  2. customwas evacuated
  3. additionfilled with nitrogen twice
  4. additionTo the mixture was added THF/H2O (10:1, 4.4 mL)
  5. temperaturecooled to room temperature
  6. additionWater (2 mL) was added
  7. extractionthe reaction was extracted with CH2Cl2 twice
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by silica gel chromatography (MeOH/CH2Cl2+1% Et3N)

Sources & evidence

ORD record
ord-a56f2b5c132e45e9b91406bcbfb0c787
Source dataset
uspto-grants-2014_09
Patent number
US08846947B2

Reaction notes

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