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

HRID 1512505Notes

Reaction equation

HRID 1512505 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:21]2([C:25]([O:27]CC)=[O:26])[CH2:24][CH2:23][CH2:22]2)[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]([C:21]2([C:25]([OH:27])=[O:26])[CH2:22][CH2:23][CH2:24]2)[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 57995657HCID 57995657, compound

Product 1

HCID 579954871-(5-Chloro-4'-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acidYield 66.3%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A mixture of ethyl 1-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutanecarboxylate (300 mg, 0.70 mmol) and lithium hydroxide monohydrate (280 mg, 11.6 mmol) in a 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 1-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid (185 mg, 66%) as white solid. 1HNMR (CDCl3): 7.42 (m, 2H); 7.32 (s, 1H), 7.23 (d, 2H), 7.18 (s, 1H), 3.87 (q, 2H); 2.85 (m, 2H), 2.54 (m, 2H), 2.39 (s, 3H), 2.12 (m, 1H); 1.83 (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-21591c4518214a97b528b0a9b13b5bb4
Source dataset
uspto-grants-2012_07
Patent number
US08217064B2

Reaction notes

Loading…