Lithium Hydroxide → 2-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid

HRID 1183708Notes

Reaction equation

HRID 1183708 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:6][C:5]([CH:18]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:19]([O:21]CC)=[O:20])=[CH:4][C:3]=1[O:28][CH2:29][C:30]([F:33])([F:32])[F:31].[Li+].[OH-]>CO.C1COCC1.O>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=2)=[CH:6][C:5]([CH:18]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:19]([OH:21])=[O:20])=[CH:4][C:3]=1[O:28][CH2:29][C:30]([F:31])([F:32])[F:33]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 57995615Ethyl 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate

Product 1

HCID 441330482-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acidYield 72.5%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Ethyl 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (320 mg, 0.647 mmol) was dissolved in a MeOH/THF/H2O (10 mL/10 mL/5 mL) mixture, LiOH (163 mg, 3.88 mmol) was added. The reaction mixture was stirred at room temperature for 5 h and then concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and evaporated under reduced pressure. Purification was achieved by re-crystallization in hexane/ether mixture to give 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (220 mg) as a white solid. 1H-NMR (500 MHz, CDCl3): 7.74 (d, 2H), 7.55 (d, 2H), 7.01 (s, 2H), 4.44 (q, 2H), 3.68 (t, 1H), 1.98 (m, 2H), 1.61 (m, 1H), 1.54 (m, 1H), 0.95 (d, 6H)

Workup

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. additionWater (10 mL) was added
  4. extractionthe reaction mixture was extracted with EtOAc (3×10 mL)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customPurification
  9. customwas achieved by re-crystallization in hexane/ether mixture

Sources & evidence

ORD record
ord-0b22d740c53249c8b56ad5e85c33d2be
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

Loading…