Cesium carbonate → HCID 66749350, compound

HRID 882208Notes

Reaction equation

HRID 882208 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[C:13]1[CH:28]=[CH:27][C:16]2[N:17]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18](=[O:21])[N:19]([CH3:20])[C:15]=2[C:14]=1[F:29])(=O)=O.[C:32]1(B(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1COCC1>[CH3:24][C:23]([CH3:26])([CH3:25])[CH2:22][N:17]1[C:16]2[CH:27]=[CH:28][C:13]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[C:14]([F:29])[C:15]=2[N:19]([CH3:20])[C:18]1=[O:21]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic Acid2×HCID 86686106HCID 86686106, compound

Product 1

HCID 66749350HCID 66749350, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of Cesium carbonate was treated with a solution of 1-(2,2-dimethylpropyl)-4-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl trifluoromethanesulfonate (7-7, 80 mg, 0.21 mmol) and Phenylboronic acid (50.8 mg, 0.42 mmol, 2.0 eq) in anhydrous THF (5 ml). The mixture was deoxygenated, and 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex was introduced (8.5 mg, 10.4 μmol, 0.05 eq) and the mixture was irradiated in a microwave at 140 deg C. for 15 min. The reaction was not complete, so more Phenylboronic acid (26 mg, 0.24 mmol, 1.0 eq) and catalyst (8.5 mg, 10.4 μmol, 0.05 eq) was added and the reaction was irradiated again at 170 deg C. for 25 min. LC/MS showed complete conversion, so the crude maroon oil was partitioned between EtOAc (2×45 ml) and aqueous saturated NaHCO3 (55 ml), the combined organic layers were dried over Na2SO4 and concentrated, then purified via reverse-phase HPLC (Acetonitrile/Water gradient with 0.1% TFA present). The title compound, 1-(2,2-dimethylpropyl)-4-fluoro-3-methyl-5-phenyl-1,3-dihydro-2H-benzimidazol-2-one (7-8), was obtained as a brown oil with >95% purity. 1H NMR (500 MHz, CDCl3) δ 7.54-7.52 (m, 2H), 7.45 (t, 2H, J=5.86 Hz), 7.38-7.35 (m, 1H), 7.09 (t, 1H, J=5.38 Hz), 6.89 (d, 1H, J=6.35 Hz), 3.69 (s, 2H), 3.66 (s, 3H), 1.06 (s, 9H). LRMS m/z: Calc'd for C19H21FN2O (M+H) 313.4, found 313.1.

Workup

  1. customThe mixture was deoxygenated
  2. addition1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex was introduced (8.5 mg, 10.4 μmol, 0.05 eq)
  3. customthe mixture was irradiated in a microwave at 140 deg C
  4. customthe reaction was irradiated again at 170 deg C
  5. waitfor 25 min
  6. customso the crude maroon oil was partitioned between EtOAc (2×45 ml) and aqueous saturated NaHCO3 (55 ml)
  7. dry with materialthe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated
  9. custompurified via reverse-phase HPLC (Acetonitrile/Water gradient with 0.1% TFA present)

Sources & evidence

ORD record
ord-98238ed76edc416ba3777983666bfd05
Source dataset
uspto-grants-2015_03
Patent number
US08993779B2

Reaction notes

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