1-Octanol → 4-Octyloxy-3-trifluoromethylbenzoic acid

HRID 2357092Notes

Reaction equation

HRID 2357092 reaction equation
[CH2:1]([OH:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C1COCC1.CC(C)([O-])C.[K+].F[C:22]1[CH:30]=[CH:29][C:25]([C:26]([OH:28])=[O:27])=[CH:24][C:23]=1[C:31]([F:34])([F:33])[F:32]>C(OCC)(=O)C>[CH2:1]([O:9][C:22]1[CH:30]=[CH:29][C:25]([C:26]([OH:28])=[O:27])=[CH:24][C:23]=1[C:31]([F:32])([F:34])[F:33])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]

Participants

6

Reactant 4

HCID 9571-OctanolHCID 8028TetrahydrofuranHCID 5222684-Fluoro-3-(trifluoromethyl)benzoic acidHCID 23665647Potassium tert-butoxide

Product 1

HCID 533492554-Octyloxy-3-trifluoromethylbenzoic acidYield 99.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

1-octanol (315 μL, 2.0 mmol), THF (5 mL), potassium t-butoxide (5 mL, 1M solution in THF), 4-Fluoro-3-trifluoromethylbenzoic acid (417 mg, 2.0 mmol) were mixed and heated at 75° C. for 3-4 hrs. The reaction mixture was then diluted with ethyl acetate and washed with water. The water layer was acidified and extracted with ethyl acetate. The organic layer was washed with brine and dried over Na2SO4 and concentrated to afford the title compound (632 mg, HPLC purity >95%), which was used for next reaction without further purification. HPLC retention time on a C8(2) column (30×3.00 mm, 3μ) was 3.28 min with gradient 50-98% acetonitrile-H2O (0.1% trifluoroacetic acid (TFA)) in 3.5 min as mobile phase.

Workup

  1. washwashed with water
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-df7e30bc70b64c7fbc77edf08ffa9672
Source dataset
uspto-grants-2010_07
Patent number
US07759370B2

Reaction notes

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