Lithium hydroxide, monohydrate → 2-(5-Chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid

HRID 1183597Notes

Reaction equation

HRID 1183597 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]([CH2:29][CH:30]2[CH2:32][CH2:31]2)[C:24]([O:26]CC)=[O:25])[CH:5]=[C:6]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.O.[OH-].[Li+]>CO.C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]([CH2:29][CH:30]2[CH2:31][CH2:32]2)[C:24]([OH:26])=[O:25])[CH:5]=[C:6]([C:13]2[CH:14]=[CH:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=2)[C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 57995652Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate

Product 1

HCID 579956172-(5-Chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acidYield 56%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A mixture of ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (100 mg, 0.214 mmol) and lithium hydroxide monohydrate (27 mg, 0.642 mmol) in a MeOH/THF/Water solvent mixture (5 ml/5 ml5/ml) was stirred for 3 h at room temperature. Upon completion of reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with EtOAc (×2). The combined organic layers were washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid in 56% yield. (52.6 mg). 1HNMR (CDCl3): 7.71 (s, 4H); 7.42 (s, 1H); 7.23 (s, 1H); 3.68 (t, 1H); 3.41 (d, 2H); 1.93 (m, 1H); 1.77 (m, 1H); 0.97 (bs, 1H); 0.71 (bs, 1H); 0.42 (m, 4H); 0.12 (m, 2H); 0.1 (m, 2H).

Workup

  1. customUpon completion of reaction
  2. customthe volatiles were removed under reduced pressure
  3. additionThe residue was diluted with water
  4. extractionextracted with EtOAc (×2)
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by Flash Column Chromatography

Sources & evidence

ORD record
ord-faf727cb0cae4d4285ab833e932711ce
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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