Lithium hydroxide, monohydrate → 1-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-cyclobutane carboxylic acid

HRID 385380Notes

Reaction equation

HRID 385380 reaction equation
C([O:3][C:4]([C:6]1([C:10]2[CH:11]=[C:12]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[C:13]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])=[C:14]([Cl:16])[CH:15]=2)[CH2:9][CH2:8][CH2:7]1)=[O:5])C.O.[OH-].[Li+]>CO.C1COCC1.O>[Cl:16][C:14]1[CH:15]=[C:10]([C:6]2([C:4]([OH:5])=[O:3])[CH2:7][CH2:8][CH2:9]2)[CH:11]=[C:12]([C:23]2[CH:24]=[CH:25][C:26]([C:29]([F:30])([F:31])[F:32])=[CH:27][CH:28]=2)[C:13]=1[O:17][CH2:18][C:19]([F:21])([F:22])[F:20]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 57995639Ethyl-1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-cyclo butane carboxylate

Product 1

HCID 441319161-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-cyclobutane carboxylic acidYield 88%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A mixture of ethyl-1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclo butane carboxylate (400 mg, 0.83 mmol) and lithium hydroxide monohydrate (0.2 g, 8.3 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10 ml) was stirred for 3 h at room temperature. Upon completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by column chromatography to give 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclobutane carboxylic acid in 88% yield (0.21 g). 1H-NMR (CDCl3, 400 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.39 (s, 1H); 7.26 (s, 1H); 3.98 (q, 2H); 2.86 (m, 2H); 2.52 (m, 2H); 2.16 (m, 1H), 1.91 (m, 1H).

Workup

  1. customUpon completion of the reaction
  2. customthe volatiles were removed under reduced pressure
  3. additionThe residue was diluted with water
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-98da0490df564cc5a3ef0d2846c08f5b
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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