Lithium Hydroxide → 1-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylic acid

HRID 1183696Notes

Reaction equation

HRID 1183696 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:22]([O:24]CC)=[O:23])[CH2:21][CH2:20][CH2:19]2)=[CH:4][C:3]=1[O:27][CH2:28][C:29]([F:32])([F:31])[F:30].[Li+].[OH-]>CO.C1COCC1.O>[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:22]([OH:24])=[O:23])[CH2:21][CH2:20][CH2:19]2)=[CH:4][C:3]=1[O:27][CH2:28][C:29]([F:30])([F:31])[F:32]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 57995543Ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate

Product 1

HCID 441332151-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylic acidYield 79.6%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.1 g) dissolved in MeOH/THF/H2O (10 mL/10 mL/5 mL) and 70 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 evaporated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylic acid (75 mg) of the product as a white solid. 1H-NMR (500 MHz, CDCl3): 7.74 (d, 2H), 7.53 (d, 2H), 6.99 (s, 1H), 6.97 (s, 1H), 4.43 (q, 2H), 2.88 (m, 2H), 2.54 (m, 2H), 2.15 (m, 1H), 1.93 (m, 1H)

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. customevaporated under reduced pressure
  7. customPurification by column chromatography over silica gel (hexane/EtOAc 9:1)

Sources & evidence

ORD record
ord-28b836d1d4be4c76812c1e462210ae5c
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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