4-(2,2-dimethylbutyl)-2-methyl-1-trityl-1H-imidazole → 2-[4-(2,2-dimethylbutyl)-1-trityl-1H-imidazol-2-yl]-1-[4-(5-fluoropyridin-2-yl)phenyl]ethanone

HRID 216394Notes

Reaction equation

C([Li])CCC.[CH3:6][C:7]([CH3:36])([CH2:34][CH3:35])[CH2:8][C:9]1[N:10]=[C:11]([CH3:33])[N:12]([C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=1.[F:37][C:38]1[CH:39]=[CH:40][C:41]([C:44]2[CH:55]=[CH:54][C:47]([C:48](N(OC)C)=[O:49])=[CH:46][CH:45]=2)=[N:42][CH:43]=1>O1CCCC1>[CH3:6][C:7]([CH3:36])([CH2:34][CH3:35])[CH2:8][C:9]1[N:10]=[C:11]([CH2:33][C:48]([C:47]2[CH:46]=[CH:45][C:44]([C:41]3[CH:40]=[CH:39][C:38]([F:37])=[CH:43][N:42]=3)=[CH:55][CH:54]=2)=[O:49])[N:12]([C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=1

Participants

Conditions

Temperature: -78 °C

Procedure

n-Butyllithium (2.5 M in hexanes) (0.53 mL, 1.32 mmol) was added to a solution of 4-(2,2-dimethylbutyl)-2-methyl-1-trityl-1H-imidazole (360 mg, 0.88 mmol) in tetrahydrofuran (15 mL) at −78° C. dropwise. After stirring at −78° C. for 40 min, 4-(5-fluoropyridin-2-yl)-N-methoxy-N-methylbenzamide (340 mg, 1.32 mmol) in tetrahydrofuran (5 mL) was added dropwise. After warming slowly to ambient temperature, the reaction mixture was quenched with saturated aqueous ammonium chloride. The reaction mixture was partitioned between water and ethyl acetate. The organic phase was dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-20% ethyl acetate/hexane afforded 2-[4-(2,2-dimethylbutyl)-1-trityl-1H-imidazol-2-yl]-1-[4-(5-fluoropyridin-2-yl)phenyl]ethanone contaminated with an unidentified byproduct. This material was used in the next step without further purification.

Workup

temperatureAfter warming slowly to ambient temperature
customthe reaction mixture was quenched with saturated aqueous ammonium chloride
customThe reaction mixture was partitioned between water and ethyl acetate
dry with materialThe organic phase was dried (magnesium sulfate)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-96d46e947a1c423bbd0e6f2aaff59578
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193228B2

Reaction notes

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