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

HRID 340792Notes

Reaction equation

HRID 340792 reaction equation
[C:1]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:6]=[CH:5][C:4]([C:7]2[C:39]([F:40])=[CH:38][C:10]3[N:11](CC4C=CC(C5C=CC=CC=5)=CC=4)[C:12]([O:14][CH:15]4[CH2:19][CH2:18][CH:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16]4)=[N:13][C:9]=3[C:8]=2[F:41])=[CH:3][CH:2]=1.C1CC=CCC=1>CCOC(C)=O.CCO.[OH-].[OH-].[Pd+2]>[C:1]1([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:2]=[CH:3][C:4]([C:7]2[C:39]([F:40])=[CH:38][C:10]3[NH:11][C:12]([O:14][CH:15]4[CH2:19][CH2:18][CH:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16]4)=[N:13][C:9]=3[C:8]=2[F:41])=[CH:5][CH:6]=1

Participants

6

Reactant 2

HCID 123431,4-CyclohexadieneHCID 67407206Ethyl 3-{[5-(biphenyl-4-yl)-1-(biphenyl-4-ylmethyl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclopentanecarboxylate

Product 1

HCID 67406155Ethyl 3-{[5-(biphenyl-4-yl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclopentanecarboxylate

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}cyclopentanecarboxylate (0.088 g, 0.140 mmol) and Pd(OH)2 (0.026 g, 0.036 mmol) in 1.5 mL of EtOAc and 0.75 mL of EtOH was added 1,4-cyclohexadiene (0.337 mL, 3.60 mmol). The resulting black suspension was microwaved at 130° C. for 2 h, and then filtered through a Celite™ pad eluting with 100% EtOAc. The resulting filtrate was then concentrated in vacuo. Purification of the resulting residue by reverse phase Gilson™ HPLC (30-100% MeCN/H2O) gave the title compound. LCMS: calculated for C27H24F2N2O3 462.49, observed m/e 462.9 (M+H)+484.9 (M+Na) (Rt 2.45/4 min).

Workup

  1. customThe resulting black suspension was microwaved at 130° C. for 2 h
  2. filtrationfiltered through a Celite™ pad
  3. washeluting with 100% EtOAc
  4. concentrationThe resulting filtrate was then concentrated in vacuo
  5. customPurification of the resulting residue by reverse phase Gilson™ HPLC (30-100% MeCN/H2O)

Sources & evidence

ORD record
ord-33a10747e7c544ecbfd93f3d7f9508cc
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Reaction notes

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