Potassium Hydroxide → 2-(2-Chloro-6-cyclopropylmethoxy-4'-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid

HRID 385356Notes

Reaction equation

HRID 385356 reaction equation
C1(C[O:5][C:6](=[O:34])[CH:7]([C:12]2[CH:17]=[C:16]([O:18][CH2:19][CH:20]3[CH2:22][CH2:21]3)[C:15]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[C:14]([Cl:33])[CH:13]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])CC1.[OH-].[K+]>CCO.O>[Cl:33][C:14]1[CH:13]=[C:12]([CH:7]([CH2:8][CH:9]([CH3:11])[CH3:10])[C:6]([OH:34])=[O:5])[CH:17]=[C:16]([O:18][CH2:19][CH:20]2[CH2:22][CH2:21]2)[C:15]=1[C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:30])([F:31])[F:32])=[CH:25][CH:24]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 579956382-(2-Chloro-6-cyclopropylmethoxy-4'-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester

Product 1

HCID 579955772-(2-Chloro-6-cyclopropylmethoxy-4'-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acidYield 86.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

2-(2-Chloro-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.06 g, 0.12 mmol) was dissolved in a mixture of EtOH and H2O (9 mL/1 mL) and KOH (0.1 g, 1.76 mmol) was added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Then, 6 N HCl was added to adjust the pH to 5 and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 and evaporated under reduced pressure to give 2-(2-chloro-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid as a yellowish solid (0.046 g, 85%). M.p.=115-116° C. 1H NMR (300 MHz, CDCl3/TMS): δ 7.67 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 7.08 (s, 1H), 6.85 (s, 1H), 3.77 (d, J=6.4 Hz, 2H), 3.65 (t, J=7.7 Hz, 1H), 2.04-1.94 (m, 1H), 1.75-1.66 (m, 1H), 1.60-1.52 (m, 1H), 1.15-0.89 (m, 1H), 0.95 (d, J=6.4 Hz, 6H), 0.54-0.40 (m, 2H), 0.20-0.10 (m, 2H). 13C NMR (75 MHz, CDCl3/TMS): δ 179.0, 157.1, 140.3, 138.8, 133.8, 130.8, 129.3 (q), 128.2, 124.6, 124.3 (q, 1JCF=271.0 Hz), 121.6, 111.2, 73.4, 49.4, 42.0, 25.9, 22.6, 22.3, 10.0, 3.0.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was refluxed for 2 h
  3. temperatureafter cooling the solvent
  4. customwas evaporated
  5. additionThen, 6 N HCl was added
  6. extractionthe reaction mixture was extracted with EtOAc (3×10 mL)
  7. dry with materialThe combined organic phases were dried over MgSO4
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-8b1ecaac846c495cb1b6e96cc6861180
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

Loading…