1,4-Cyclohexadiene → Ethyl 3-{[5-(biphenyl-4-yl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclobutane carboxylate

HRID 340796Notes

Reaction equation

HRID 340796 reaction equation
[C:1]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:6]=[CH:5][C:4]([C:7]2[C:38]([F:39])=[CH:37][C:10]3[N:11](CC4C=CC(C5C=CC=CC=5)=CC=4)[C:12]([O:14][CH:15]4[CH2:18][CH:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:16]4)=[N:13][C:9]=3[C:8]=2[F:40])=[CH:3][CH:2]=1.C1CC=CCC=1>CCOC(C)=O.CCO.[OH-].[OH-].[Pd+2]>[C:1]1([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:2]=[CH:3][C:4]([C:7]2[C:38]([F:39])=[CH:37][C:10]3[NH:11][C:12]([O:14][CH:15]4[CH2:18][CH:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:16]4)=[N:13][C:9]=3[C:8]=2[F:40])=[CH:5][CH:6]=1

Participants

6

Reactant 2

HCID 123431,4-CyclohexadieneHCID 67407044Ethyl 3-{[5-(biphenyl-4-yl)-1-(biphenyl-4-ylmethyl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclobutanecarboxylate

Product 1

HCID 67405225Ethyl 3-{[5-(biphenyl-4-yl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclobutane carboxylate

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 3-{[5-(biphenyl-4-yl)-1-(biphenyl-4-ylmethyl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclobutanecarboxylate (0.160 g, 0,260 mmol) and Pd(OH)2 (0.048 g, 0.068 mmol) in 2.5 mL of EtOAc and 1.25 mL of EtOH was added 1,4-cyclohexadiene (0.630 mL, 6.70 mmol). The resulting black suspension was microwaved at 130° C. for 2 h. Then the reaction was filtered through a Celite™ pad, washed with 100% EtOAc, and the filtrate was concentrated in vacuo. Purification of the resulting residue by reverse phase Gilson™ HPLC (50-100% MeCN/H2O) afforded the title compound as a white solid. LCMS: calculated for C26H22F2N2O3 448.46, observed m/e 449.0 (M+H)+ (Rt 2.27/4 min).

Workup

  1. customThe resulting black suspension was microwaved at 130° C. for 2 h
  2. filtrationThen the reaction was filtered through a Celite™ pad
  3. washwashed with 100% EtOAc
  4. concentrationthe filtrate was concentrated in vacuo
  5. customPurification of the resulting residue by reverse phase Gilson™ HPLC (50-100% MeCN/H2O)

Sources & evidence

ORD record
ord-07062191be3a4e298301f7f76f55b0fc
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Reaction notes

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