Methanol → 2-(5-Chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoic acid

HRID 1183754Notes

Reaction equation

HRID 1183754 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]([CH2:29][C:30]([F:33])([F:32])[F:31])[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.CO.O.O[Li].O>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]([CH2:29][C:30]([F:31])([F:32])[F:33])[C:24]([OH:26])=[O:25])[CH:5]=[C:6]([C:13]2[CH:14]=[CH:15][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:17][CH:18]=2)[C:7]=1[O:8][CH2:9][CH:10]1[CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 57995541Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoate

Product 1

HCID 579954962-(5-Chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoate (0.1 g, 0.404 mmol) in a mixture of THF (10 mL), methanol (10 mL) and water (5 mL) was added LiOH.H2O (85 mg, 2.024 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of the starting material as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL) the combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4 and evaporated under vacuum. The crude material was purified by column chromatography to 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoic acid (38 mg) as sticky syrup. 1HNMR (500 MHz) (CDCl3): δ (ppm) 7.71 (m, 4H), 7.39 (s, 1H), 7.19 (s, 1H), 3.92 (m, 1H), 3.41 (d, 2H), 3.08 (m, 1H), 2.54 (m, 1H), 0.96 (m, 1H), 0.40 (d, 2H), 0.00 (m, 2H).

Workup

  1. customAfter complete consumption of the starting material
  2. additionthe reaction mixture was diluted with water (10 mL)
  3. customat 0° C
  4. extractionThe aqueous layer was extracted with EtOAc (2×20 mL) the combined organic extracts
  5. washwere washed with water (10 mL), brine (20 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. customevaporated under vacuum
  8. customThe crude material was purified by column chromatography to 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoic acid (38 mg) as sticky syrup

Sources & evidence

ORD record
ord-a01307edec944d29b2a139daf8e814fb
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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