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

HRID 385447Notes

Reaction equation

HRID 385447 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]([CH2:27][CH:28]2[CH2:30][CH2:29]2)[C:22]([O:24]CC)=[O:23])[CH:5]=[C:6]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].O.[OH-].[Li+]>CO.C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]([CH2:27][CH:28]2[CH2:30][CH2:29]2)[C:22]([OH:24])=[O:23])[CH:5]=[C:6]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 57995605Ethyl 2-(5-chloro-4'-methyl-6-(2,2,2-trifluoroethoxy) biphenyl-3-yl)-3-cyclopropylpropanoate

Product 1

HCID 441320782-(5-Chloro-4'-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoic acidYield 57.7%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A mixture of ethyl 2-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy) biphenyl-3-yl)-3-cyclopropylpropanoate (370 mg, 0.84 mmol) and lithium hydroxide monohydrate (282 mg, 6.7 mmol) in MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After 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 (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoic acid (200 mg) as a white solid. 1HNMR (CDCl3): 7.21-7.42 (m, 6H); 3.87 (q, 2H); 3.65 (t, 1H); 2.39 (s, 3H), 1.93 (m, 1H); 1.88 (m, 1H); 0.66 (m, 1H); 0.42 (m, 2H); 0.12 (m, 1H); 0.1 (m, 1H).

Workup

  1. customAfter completion of the reaction
  2. customthe volatiles were removed under reduced pressure
  3. additionThe residue was diluted with water
  4. extractionextracted with ethyl acetate (2×25 mL)
  5. washThe combined organic layers were washed with water
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by Flash Column Chromatography

Sources & evidence

ORD record
ord-7d91bbcdf9be4edfade4155a5dc5caec
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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