Ethyl 5-[4-(methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indole-2-carboxylate → 5-[4-(Methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indole-2-carboxylic acid

HRID 1188885Notes

Reaction equation

HRID 1188885 reaction equation
[CH3:1][S:2]([C:5]1[CH:33]=[CH:32][C:8]([O:9][C:10]2[CH:11]=[C:12]3[C:16](=[C:17]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH:18]=2)[NH:15][C:14]([C:27]([O:29]CC)=[O:28])=[CH:13]3)=[CH:7][CH:6]=1)(=[O:4])=[O:3]>O1CCCC1.C(O)C.[OH-].[Na+]>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:9][C:10]2[CH:11]=[C:12]3[C:16](=[C:17]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH:18]=2)[NH:15][C:14]([C:27]([OH:29])=[O:28])=[CH:13]3)=[CH:32][CH:33]=1)(=[O:3])=[O:4]

Participants

5

Reactant 1

HCID 66898356Ethyl 5-[4-(methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indole-2-carboxylate

Product 1

HCID 668978135-[4-(Methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indole-2-carboxylic acidYield 33.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 5-[4-(methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indole-2-carboxylate (3.5 g) was dissolved in a mixed solvent of tetrahydrofuran (30 mL)-ethanol (30 mL), 1M aqueous sodium hydroxide solution (15 mL) was added, and the mixture was stirred at 50° C. for 1 hr. The reaction solution was allowed to cool to room temperature, and concentrated under reduced pressure. Water was added to the residue, and the mixture was neutralized with 1M hydrochloric acid, and subjected to extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained crude product was crystallized from a mixed solvent of ethanol-hexane-diethyl ether. The obtained colorless crystals were recrystallized from acetone-hexane to give the title compound (1.1 g) as colorless crystals. melting point 256-258° C. (decomposition).

Workup

  1. additionwas added
  2. temperatureto cool to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionWater was added to the residue
  5. extractionsubjected to extraction with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained crude product
  11. customwas crystallized from a mixed solvent of ethanol-hexane-diethyl ether
  12. customThe obtained colorless crystals were recrystallized from acetone-hexane

Sources & evidence

ORD record
ord-ee20c4cbabf942a2bb9b31cf19e34e06
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

Loading…