Hydrochloric Acid → HCID 66699393, compound

HRID 1096044Notes

Reaction equation

HRID 1096044 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([OH:9])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:25])[C:11]([C:17]1[CH:18]=[CH:19][C:20](=[O:24])[N:21]([CH3:23])[CH:22]=1)([OH:16])[C:12]([F:15])([F:14])[F:13].[CH2:26]([O:28][C:29](=[O:34])[C:30](Br)([CH3:32])[CH3:31])[CH3:27].[OH-].[Na+].Cl>CC(N(C)C)=O>[CH2:26]([O:28][C:29](=[O:34])[C:30]([O:9][C:6]1[CH:5]=[CH:4][C:3]([CH:10]([CH3:25])[C:11]([OH:16])([C:17]2[CH:18]=[CH:19][C:20](=[O:24])[N:21]([CH3:23])[CH:22]=2)[C:12]([F:15])([F:13])[F:14])=[C:2]([Cl:1])[C:7]=1[Cl:8])([CH3:32])[CH3:31])[CH3:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl ester2×HCID 14798Sodium Hydroxide2×HCID 57421326HCID 57421326, compound

Product 1

HCID 66699393HCID 66699393, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

5-[2-(2,3-Dichloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1-methyl-1H-pyridin-2-one (Example 197, step 5; 198 mg, 0.50 mmol) and 2-bromo-2-methyl-propionic acid ethyl ester (0.23 mL, 1.5 mmol), were dissolved in 1 ml dimethylacetamide and treated with 60 mg NaOH (finely powdered). After 3 h stirring at rt 2-bromo-2-methyl-propionic acid ethyl ester (0.11 mL, 0.75 mmol) was added, followed by 30 mg NaOH (finely powdered). After 19 h stirring at rt, the reaction mixture was poured on ice-water (10 mL) and the pH adjusted to 3 with aqueous 2N HCl. The reaction mixture was then extracted twice with ethyl acetate, the combined organic phases washed with water and brine, dried over magnesium sulfate, filtered-off and concentrated in vacuo. The residue was purified by flash chromatography (8 g SiO2, EtOAc/heptane 2:1) to give 118 mg of the title compound as colorless viscous oil. MS (M+H+)=510.2

Workup

  1. additionwas added
  2. additionthe reaction mixture was poured on ice-water (10 mL)
  3. extractionThe reaction mixture was then extracted twice with ethyl acetate
  4. washthe combined organic phases washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationfiltered-off and concentrated in vacuo
  7. customThe residue was purified by flash chromatography (8 g SiO2, EtOAc/heptane 2:1)

Sources & evidence

ORD record
ord-22fb468249b049e0995782ea1d58ff9a
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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