Hydrochloric Acid → 5-Chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzoic acid

HRID 1849598Notes

Reaction equation

HRID 1849598 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1([CH2:8][OH:9])[CH2:7][CH2:6][CH2:5][CH2:4]1.CC(C)([O-])C.[K+].[Cl:18][C:19]1[C:20](F)=[CH:21][C:22]([F:28])=[C:23]([CH:27]=1)[C:24]([OH:26])=[O:25].Cl>CS(C)=O>[Cl:18][C:19]1[C:20]([O:9][CH2:8][C:3]2([C:2]([F:10])([F:11])[F:1])[CH2:7][CH2:6][CH2:5][CH2:4]2)=[CH:21][C:22]([F:28])=[C:23]([CH:27]=1)[C:24]([OH:26])=[O:25]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 148764175-Chloro-2,4-difluorobenzoic acidHCID 23665647Potassium tert-butoxideHCID 86703453(1-(Trifluoromethyl)cyclopentyl)methanol

Product 1

HCID 867034525-Chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzoic acidYield 88.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of (1-(trifluoromethyl)cyclopentyl)methanol (2.80 g, 16.65 mmol) in anhydrous dimethylsulfoxide (50 ml) was added potassium tert-butoxide (4.50 g, 40.106 mmol) and the reaction mixture was stirred at ambient temperature for 30 minutes. 5-chloro-2,4-difluorobenzoic acid (3.20 g, 16.62 mmol) was added to the reaction mixture, and stirring was continued for 2 hours. The reaction mixture was acidified to pH=1 with 5% aqueous hydrochloric acid solution and extracted with ethyl acetate, the combined organic extracts was washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (30% ethyl acetate in hexanes) afforded the title compound (5.00 g, 88%) containing o-substituted regioisomer, which was used for next step without further purification: MS (ES−) m/z 339.2, 341.2 (M−1).

Workup

  1. stirringstirring
  2. waitwas continued for 2 hours
  3. extractionextracted with ethyl acetate
  4. washthe combined organic extracts was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by column chromatography (30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2f45f00aa4254b3b8dece2868a5c0cf6
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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