Methanol → HCID 68733423, compound

HRID 1183751Notes

Reaction equation

HRID 1183751 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:24]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:25]([O:27]CC)=[O:26])[CH:6]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[C:8]=1[O:9][CH2:10][CH:11]1[CH2:13][CH2:12]1)#[N:2].CO.O.O[Li].O>C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([CH:24]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:25]([OH:27])=[O:26])[CH:6]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:21])([F:23])[F:22])=[CH:16][CH:15]=2)[C:8]=1[O:9][CH2:10][CH:11]1[CH2:12][CH2:13]1)#[N:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 68733665HCID 68733665, compound

Product 1

HCID 68733423HCID 68733423, compoundYield 42.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 2-(5-cyano-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.125 g, 0.272 mmol) in a mixture of THF (5 mL), methanol (5 mL) and water (2 mL) was added LiOH.H2O (34 mg, 0.816 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 and concentrated under reduced pressure. The crude material was purified by column chromatography to afford 2-(5-cyano-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (50 mg) as an off white solid. 1HNMR (500 MHz) (CDCl3): δ (ppm) 7.70 (m, 4H), 7.61 (s, 1H), 7.51 (s, 1H), 3.71 (t, 1H), 3.55 (m, 2H), 2.00 (m, 1H), 1.67 (m, 1H), 1.51 (m, 1H), 1.02 (m, 1H), 0.91 (d, 6H), 0.45 (m, 2H), 0.05 (m, 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. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-4380fb5c1d024f1b987e248982258bba
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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