Ethanol → Fasiglifam

HRID 1848788Notes

Reaction equation

HRID 1848788 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:5]=[C:4]([CH3:16])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][C:25]2[CH:37]=[CH:36][C:28]3[C:29]([CH2:32][C:33]([OH:35])=[O:34])=[CH:30][O:31][C:27]=3[CH:26]=2)[CH:18]=1.C(O)C>C(N(CC)CC)C>[CH3:16][C:4]1[CH:5]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:7]=[C:2]([CH3:1])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][C:25]2[CH:37]=[CH:36][C:28]3[C@H:29]([CH2:32][C:33]([OH:35])=[O:34])[CH2:30][O:31][C:27]=3[CH:26]=2)[CH:18]=1

Participants

4

Reactant 2

HCID 702EthanolHCID 86706791[6-({2',6'-Dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-1-benzofuran-3-yl]acetic acid

Product 1

HCID 24857286FasiglifamYield 99.8%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

Under an argon atmosphere, to [6-({2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-1-benzofuran-3-yl]acetic acid (522 mg), dichloro[(+)-1,2-bis((2R,5R)-2,5-diisopropylphosphorano)benzene]ruthenium (II)-N,N-dimethylformamide complex (7.4 mg) in an autoclave container was added a solution of dehydrated ethanol (6 mL) containing triethylamine (0.139 mL), and the mixture was stirred at 50° C. for 24 hr under a hydrogen atmosphere (1 MPa). The reaction mixture was concentrated, 10% aqueous citric acid solution (25 mL) and ethyl acetate (25 mL) were added, and an extraction operation was performed. The aqueous layer was extracted with ethyl acetate (25 mL), and the combined organic layer was washed with water (25 mL), dried over sodium sulfate and concentrated. The crude product was washed with diisopropyl ether. After filtration, the obtained solid was dried at 50° C. under reduced pressure to give the title compound (523 mg) as white crystals. 80.0% ee.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. addition10% aqueous citric acid solution (25 mL) and ethyl acetate (25 mL) were added
  3. extractionThe aqueous layer was extracted with ethyl acetate (25 mL)
  4. washthe combined organic layer was washed with water (25 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. washThe crude product was washed with diisopropyl ether
  8. filtrationAfter filtration
  9. customthe obtained solid was dried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-c50cb3cecb53416cb03b2fc816d45bda
Source dataset
uspto-grants-2015_02
Patent number
US08952185B2

Reaction notes

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