Hydrochloric Acid → 2-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-methyl-propionamide

HRID 333823

Reaction equation

HRID 333823 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:23])[CH:5]=[CH:6][C:7]=1[CH:8]([CH3:22])[C:9]([C:15]1[CH:20]=[CH:19][N:18]=[C:17]([Cl:21])[CH:16]=1)([OH:14])[C:10]([F:13])([F:12])[F:11].Br[C:25]([CH3:30])([CH3:29])[C:26]([NH2:28])=[O:27].[OH-].[Na+].Cl>CC(N(C)C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[CH:8]([CH3:22])[C:9]([C:15]1[CH:20]=[CH:19][N:18]=[C:17]([Cl:21])[CH:16]=1)([OH:14])[C:10]([F:13])([F:12])[F:11])[O:23][C:25]([CH3:30])([CH3:29])[C:26]([NH2:28])=[O:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 1012352-Bromo-2-methylpropanamide2×HCID 574212643-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenol

Product 1

HCID 574212652-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-methyl-propionamide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenol (Example 133, 200 mg) and 2-bromo-2-methyl-propionamide (272 mg) in dimethyl acetamide (1 mL) were treated with sodium hydroxide (66 mg) and stirred at r.t. for 17 h. A second portion of 2-bromo-2-methyl-propionamide (272 mg) followed by sodium hydroxide (66 mg) was added and the reaction mixture further stirred for 2 h at r.t. This process was repeated a last time and the reaction mixture was diluted with ice-water (10 mL), neutralized with 1N aqueous HCl, extracted with ethyl acetate (2×), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (20 g silica gel, ethyl acetate/heptane 1:2) to give the title compound as off-white waxy solid (170 mg). MS (m/e)=451.0 (MH+).

Workup

  1. additionwas added
  2. stirringthe reaction mixture further stirred for 2 h at r.t
  3. extractionextracted with ethyl acetate (2×)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (20 g silica gel, ethyl acetate/heptane 1:2)

Sources & evidence

ORD record
ord-a96b5cd409304b4699b22d5d76106504
Source dataset
uspto-grants-2014_11
Patent number
US08883786B2

Linked notes

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