Propanoic acid, 2-bromo-2-methyl-, ethyl ester → HCID 89907034, compound

HRID 526693Notes

Reaction equation

HRID 526693 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH2:25][OH:26])[C:11]([CH3:24])=[N:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH2:29]([O:31][C:32](=[O:37])[C:33](Br)([CH3:35])[CH3:34])[CH3:30]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:29]([O:31][C:32](=[O:37])[C:33]([O:26][CH2:25][C:10]1[C:11]([CH3:24])=[N:12][C:13]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([F:21])([F:22])[F:23])=[CH:18][CH:19]=2)=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH:9]=1)([CH3:35])[CH3:34])[CH3:30]

Participants

6

Reactant 3

HCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 24758Sodium hydrideHCID 89907880HCID 89907880, compound

Product 1

HCID 89907034HCID 89907034, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 500 mg of [5-(4-Chloro-phenyl)-2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-methanol in 6 ml of DMF were added 264 mg of sodium hydride (60% in mineral oil) at room temperature. After 15 min 449 mg of tetrabutylammonium iodide and 1.0 g of 2-Bromo-2-methyl-propionic acid ethyl ester were added and the reaction mixture was stirred for 16 h at room temperature. After dilution with saturated aqueous sodium hydrogen carbonate solution, the reaction mixture was filtered through a chem Elut® cartridge by eluting with ethyl acetate The solvents were removed under reduced pressure and the crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate. The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 400 mg.

Workup

  1. filtrationAfter dilution with saturated aqueous sodium hydrogen carbonate solution, the reaction mixture was filtered through a chem Elut® cartridge
  2. washby eluting with ethyl acetate The solvents
  3. customwere removed under reduced pressure
  4. customthe crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate
  5. additionThe fractions containing the product
  6. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-361494585b4d48bdbf18ba547fd307e3
Source dataset
uspto-grants-2016_05
Patent number
US09346757B2

Reaction notes

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