Ethanol → HCID 44133050, compound

HRID 385372Notes

Reaction equation

HRID 385372 reaction equation
C[O:2][C:3](=[O:33])[CH:4]([C:10]1[CH:11]=[C:12]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=2)[C:13]([Cl:22])=[C:14]([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])[CH:15]=1)[CH2:5][CH:6]1[CH2:9][CH2:8][CH2:7]1.CCO.[OH-].[K+]>O>[Cl:22][C:13]1[C:12]([C:23]2[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=2)=[CH:11][C:10]([CH:4]([CH2:5][CH:6]2[CH2:9][CH2:8][CH2:7]2)[C:3]([OH:33])=[O:2])=[CH:15][C:14]=1[O:16][CH2:17][C:18]([F:19])([F:20])[F:21]

Participants

5

Reactant 3

HCID 702EthanolHCID 14797Potassium HydroxideHCID 57995544HCID 57995544, compound

Product 1

HCID 44133050HCID 44133050, compoundYield 100.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of the 2-[6-chloro-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid methyl ester (8.0 g, 14.5 mmol) in a mixture of the EtOH (100 mL) and H2O (15 mL) was added potassium hydroxide (10 g, 178.5 mmol). The reaction mixture was refluxed for 3 h and the solvent evaporated. Then, 6 N HCl was added to adjust the pH to 3-5 and the mixture was extracted with EtOAc (3×50 mL). The combined organic phases were dried over MgSO4 and evaporated to give 2-[6-chloro-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid as a white solid (7.0 g, 90%). 1H NMR (300 MHz, CDCl3/TMS): δ 7.70 (d, J=8.2 Hz, 2H), 7.53 (d, J=8.2 Hz, 2H), 6.98 (s, 2H), 4.47 (q, J=8.0 Hz, 2H), 3.49 (t, J=7.7 Hz, 1H), 2.27-2.13 (m, 2H), 2.06-1.73 (m, 5H), 1.71-1.52 (m, 2H). 13C NMR (75 MHz, CDCl3/TMS): δ 179.1, 153.6, 142.1, 141.2, 138.0, 129.7, 125.0 (q, 3JCF=3.6 Hz), 124.9, 124.0 (q, 1JCF=262.5 Hz), 123.0 (q, 1JCF=277.6 Hz), 121.8, 114.3, 67.3 (q, 1JCF=36.0 Hz), 49.3, 40.3, 33.9, 28.3, 28.0, 18.5.

Workup

  1. temperatureThe reaction mixture was refluxed for 3 h
  2. customthe solvent evaporated
  3. additionThen, 6 N HCl was added
  4. extractionthe mixture was extracted with EtOAc (3×50 mL)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. customevaporated

Sources & evidence

ORD record
ord-c19783660f1c454f9ea55b4d4a663d17
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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