Potassium Carbonate → Ethyl 4-{[5-(biphenyl-4-yl)-1-(biphenyl-4-ylmethyl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclohexanecarboxylate

HRID 340786Notes

Reaction equation

HRID 340786 reaction equation
[C:1]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:12]3[CH:13]=[C:14]([F:19])[C:15](I)=[C:16]([F:17])[C:11]=3[N:10]=[C:9]2[O:20][CH:21]2[CH2:26][CH2:25][CH:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][CH2:22]2)=[CH:3][CH:2]=1.[C:38]1([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[C:38]1([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:43]=[CH:42][C:41]([C:15]2[C:14]([F:19])=[CH:13][C:12]3[N:8]([CH2:7][C:4]4[CH:5]=[CH:6][C:1]([C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=5)=[CH:2][CH:3]=4)[C:9]([O:20][CH:21]4[CH2:22][CH2:23][CH:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:25][CH2:26]4)=[N:10][C:11]=3[C:16]=2[F:17])=[CH:40][CH:39]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1512531,1'-Biphenyl-4-yl-boronic acidHCID 67407825ethyl 4-{[1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-1H-benzimidazol-2-yl]oxy}cyclohexane carboxylate

Product 1

HCID 67406617Ethyl 4-{[5-(biphenyl-4-yl)-1-(biphenyl-4-ylmethyl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclohexanecarboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A 250 mL flask was charged with ethyl 4-{[1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-1H-benzimidazol-2-yl]oxy}cyclohexane carboxylate (2 g, 3.24 mmol), 4-Biphenylboronic acid (0.700 g, 3.53 mmol), Pd(PPh3)4 (0.185 g, 0.160 mmol), DMF (30 mL), and 1 M aqueous K2CO3 (6.5 ml, 6.50 mmol). The reaction was degassed with N2 and then heated at 120° C. for 1 hour. The volatiles were removed in vacuo and the resulting residue was partitioned between EtOAc and H2O. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated. Chromatography of the resulting residue over silica eluting with 15% [EtOAc:DCM (1:1)]/hexanes afforded the desired trans product as white solid. LC-MS: calculated for C41H36F2N2O3 642.27, observed m/e: 643.14 (M+H)+ (Rt 3.07/4 min).

Workup

  1. customThe reaction was degassed with N2
  2. customThe volatiles were removed in vacuo
  3. customthe resulting residue was partitioned between EtOAc and H2O
  4. extractionThe aqueous phase was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customChromatography of the resulting residue over silica eluting with 15% [EtOAc:DCM (1:1)]/hexanes afforded the desired trans product as white solid
  10. custom643.14 (M+H)+ (Rt 3.07/4 min)

Sources & evidence

ORD record
ord-330d96429e8f460095b12288b7d8a88b
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Reaction notes

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