1,3-Cyclohexadiene → 5-[4,6-Difluoro-5-(1-methyl-1H-indol-5-yl)-1H-benzoimidazol-2-yloxy]-2-methyl-benzoic acid methyl ester

HRID 1945297Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:46])[C:4]1[CH:9]=[C:8]([O:10][C:11]2[N:15](CC3C=CC(C4C=CC=CC=4)=CC=3)[C:14]3[CH:29]=[C:30]([F:44])[C:31]([C:34]4[CH:35]=[C:36]5[C:40](=[CH:41][CH:42]=4)[N:39]([CH3:43])[CH:38]=[CH:37]5)=[C:32]([F:33])[C:13]=3[N:12]=2)[CH:7]=[CH:6][C:5]=1[CH3:45].C1CCC=CC=1>[OH-].[OH-].[Pd+2].CCOC(C)=O.CCO>[CH3:1][O:2][C:3](=[O:46])[C:4]1[CH:9]=[C:8]([O:10][C:11]2[NH:15][C:14]3[CH:29]=[C:30]([F:44])[C:31]([C:34]4[CH:35]=[C:36]5[C:40](=[CH:41][CH:42]=4)[N:39]([CH3:43])[CH:38]=[CH:37]5)=[C:32]([F:33])[C:13]=3[N:12]=2)[CH:7]=[CH:6][C:5]=1[CH3:45]

Participants

Conditions

Temperature: 130 °C

Procedure

A solution of 5-[1-biphenyl-4-ylmethyl-4,6-difluoro-5-(1-methyl-1H-indol-5-yl)-1H-benzoimidazol-2-yloxy]-2-methyl-benzoic acid methyl ester (900 mg, 1.467 mmol) and Pearlman's catalyst (20% Pd(OH)2 on carbon) (180 mg) in EtOAc-EtOH (2:1, 7 mL) was treated with cyclohexadiene (2351 mg), and the resulting reaction mixture was heated under microwave at 130° C. for 10 min, and then at 130° C. for another 10 min. The cooled reaction mixture was filtered through a Celite pad (washed with 10% MeOH—CH2Cl2), and the filtrate was absorbed onto silica gel and purified by ISCO flash chromatography to give desired product as a white foam.

Workup

customthe resulting reaction mixture
customThe cooled reaction mixture
filtrationwas filtered through a Celite pad (washed with 10% MeOH—CH2Cl2)
customthe filtrate was absorbed onto silica gel
custompurified by ISCO flash chromatography

Sources & evidence

ORD record: ord-5af95ca5fae14a6d927b42ac341291bf
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394969B2

Reaction notes

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