Lithium Hydroxide → HCID 58201228, compound

HRID 1944407Notes

Reaction equation

HRID 1944407 reaction equation
C[O:2][C:3](=[O:31])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([F:14])=[CH:11][CH:12]=2)[C:7]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[S:22]([C:25]2[S:26][CH:27]=[CH:28][CH:29]=2)(=[O:24])=[O:23])=[C:6]1[CH3:30].O1CCCC1.[OH-].[Li+]>O>[F:14][C:10]1[CH:9]=[C:8]2[C:13](=[CH:12][CH:11]=1)[N:5]([CH2:4][C:3]([OH:31])=[O:2])[C:6]([CH3:30])=[C:7]2[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([C:25]1[S:26][CH:27]=[CH:28][CH:29]=1)(=[O:23])=[O:24]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 67044315HCID 67044315, compound

Product 1

HCID 58201228HCID 58201228, compoundYield 68.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of {5-fluoro-2-methyl-3-[2-(thiophene-2-sulfonyl)benzyl]indol-1-yl}acetic acid methyl ester (0.21 g) and tetrahydrofuran (5.0 mL) was treated with 1.0 M aqueous lithium hydroxide solution (1.2 mL), and the resulting mixture was stirred at room temperature for 2 hours. The mixture was diluted with water (25 mL), concentrated to low bulk under reduced pressure and the pH adjusted to 4 by the addition of 0.1 M aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate and the combined organic extract was washed with saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of dichloromethane and ethyl acetate containing 0.1% formic acid (1:0 to 0:1 by volume), followed by preparative reverse-phase HPLC, eluting with a mixture of acetonitrile and water (3:7 to 9:1 by volume) to afford the title compound as a white solid (0.14 g).

Workup

  1. concentrationconcentrated to low bulk under reduced pressure
  2. additionthe pH adjusted to 4 by the addition of 0.1 M aqueous hydrochloric acid solution
  3. extractionThe mixture was extracted with ethyl acetate
  4. extractionthe combined organic extract
  5. washwas washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customthe residue purified by column chromatography on silica gel
  9. washeluting with a mixture of dichloromethane and ethyl acetate containing 0.1% formic acid (1:0 to 0:1 by volume)
  10. washeluting with a mixture of acetonitrile and water (3:7 to 9:1 by volume)

Sources & evidence

ORD record
ord-a8c010a0e60348b7badf5ec7cddc6866
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Reaction notes

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