Cesium carbonate → HCID 86721355, compound

HRID 869526Notes

Reaction equation

HRID 869526 reaction equation
[O:1]([CH2:9][C:10]1[N:14]([CH2:15][C:16]2[CH:35]=[CH:34][C:19]3/[C:20](=[C:30](/[CH3:33])\[C:31]#[N:32])/[C:21]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:22]=4[O:23][CH2:24][C:18]=3[CH:17]=2)[C:13]2[CH:36]=[CH:37][CH:38]=[C:39]([OH:40])[C:12]=2[N:11]=1)[Si](C(C)(C)C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:48]([F:53])([F:52])C([O-])=O.[Na+].[Cl-].[NH4+]>CN(C=O)C>[F:52][CH:48]([F:53])[O:40][C:39]1[C:12]2[N:11]=[C:10]([CH2:9][OH:1])[N:14]([CH2:15][C:16]3[CH:35]=[CH:34][C:19]4/[C:20](=[C:30](/[CH3:33])\[C:31]#[N:32])/[C:21]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:22]=5[O:23][CH2:24][C:18]=4[CH:17]=3)[C:13]=2[CH:36]=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 2734985Sodium chlorodifluoroacetateHCID 86721354HCID 86721354, compound

Product 1

HCID 86721355HCID 86721355, compoundYield 31.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

[step 2] (E)-2-[8-({2-[(tert-butyldimethylsiloxy)methyl]-4-hydroxy-1H-benzo[d]imidazol-1-yl}methyl)-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene]propanenitrile (200 mg, 0.36 mmol) obtained in step 1 was dissolved in DMF (5.5 mL), cesium carbonate (352 mg, 1.08 mmol) and sodium 2-chloro-2,2-difluoroacetate (165 mg, 1.08 mmol) were added, and the mixture was stirred at 60° C. for 1 hr. To the mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted 3 times with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 v/v-20/80 v/v) to give (E)-2-(8-{[4-(difluoromethoxy)-2-(hydroxymethyl)-1H-benzo[d]imidazol-1-yl]methyl}-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene)propanenitrile (55 mg, 31%).

Workup

  1. extractionthe mixture was extracted 3 times with ethyl acetate
  2. washThe combined organic layers were washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 v/v-20/80 v/v)

Sources & evidence

ORD record
ord-53d60efbca9b4ef7b65683a4a7243db8
Source dataset
uspto-grants-2015_03
Patent number
US08969345B2

Reaction notes

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