Lithium Hydroxide → 1-(6-Chloro-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclopentane carboxylic acid

HRID 385418Notes

Reaction equation

HRID 385418 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]([C:18]2([C:23]([O:25]CC)=[O:24])[CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:4][C:3]=1[O:28][CH2:29][CH:30]1[CH2:32][CH2:31]1.[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]([C:18]2([C:23]([OH:25])=[O:24])[CH2:19][CH2:20][CH2:21][CH2:22]2)=[CH:4][C:3]=1[O:28][CH2:29][CH:30]1[CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 57995610Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate

Product 1

HCID 579955961-(6-Chloro-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclopentane carboxylic acidYield 59.8%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate (80 mg) dissolved in 10 mL of MeOH/THF/H2O (10 mL/10 mL/5 mL) and 57 mg LiOH added. The reaction mixture was stirred at room temperature for 5 h and 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 concentrated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentane carboxylic acid (45 mg) as a white solid. 1H-NMR (500 MHz, CDCl3): 7.68 (d, 2H), 7.55 (d, 2H), 6.99 (s, 1H), 6.97 (s, 1H), 3.97 (d, 2H), 2.64 (m, 2H), 1.95 (m, 2H), 1.77 (m, 4H), 1.21 (m, 1H), 0.45 (m, 2H), 0.18 (m, 2H);

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionWater (10 mL) was added
  3. extractionthe reaction mixture was extracted with EtOAc (3×10 mL)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography over silica gel (hexane/EtOAc 9:1)

Sources & evidence

ORD record
ord-c93b4f0c84a941df921c93abbd25e399
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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