Methanol → HCID 57995555, compound

HRID 385483Notes

Reaction equation

HRID 385483 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[C:11]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=3)=[CH:10][C:9]([CH:22]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:23]([O:25]CC)=[O:24])=[CH:8][C:7]=2[S:32][CH3:33])[CH2:3][CH2:2]1.CO.O.O[Li].O>C1COCC1>[CH:1]1([CH2:4][O:5][C:6]2[C:11]([C:12]3[CH:13]=[CH:14][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:17]=3)=[CH:10][C:9]([CH:22]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:23]([OH:25])=[O:24])=[CH:8][C:7]=2[S:32][CH3:33])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 57995500HCID 57995500, compound

Product 1

HCID 57995555HCID 57995555, compoundYield 50.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 2-(6-(cyclopropylmethoxy)-5-(methylthio)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (80 mg, 0.166 mmol) in a mixture of THF (10 mL), methanol (10 mL) and water (5 mL) was added LiOH.H2O (20 mg, 0.832 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of 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); combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuo. The crude material was purified by column chromatography to afford 2-(6-(cyclopropylmethoxy)-5-(methylthio)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (38 mg) as an off white solid. 1HNMR (500 MHz) (CDCl3): δ (ppm) 7.75 (d, 2H), 7.65 (d, 2H), 7.31 (s, 1H), 7.23 (s, 1H), 3.65 (t, 1H), 3.60 (d, 2H), 2.82 (s, 3H), 1.98 (m, 1H), 1.65 (m, 1H), 1.5 (m, 1H), 1.22 (m, 1H), 0.9 (d, 6H), 0.38 (d, 2H), 0.01 (d, 2H).

Workup

  1. customAfter complete consumption of 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)
  5. washcombined organic extracts were washed with water (10 mL), brine (20 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuo
  9. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-f9afbb7d093e40948b14cdb9c6df2156
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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