Tetrahydrofuran → HCID 10175276, compound

HRID 351019Notes

Reaction equation

HRID 351019 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]1[S:14]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][CH2:26][O:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:30][C:29]=2[CH2:41][CH2:42][CH3:43])=[CH:19][CH:18]=1)(=[O:16])=[O:15])=[O:4].[OH-].[Na+].O1CCCC1>CO>[O:34]([C:31]1[CH:32]=[CH:33][C:28]([O:27][CH2:26][CH2:25][CH2:24][O:23][C:20]2[CH:21]=[CH:22][C:17]([S:14]([N:6]3[C:7]4[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=4)[CH2:13][C@@H:5]3[C:3]([OH:4])=[O:2])(=[O:16])=[O:15])=[CH:18][CH:19]=2)=[C:29]([CH2:41][CH2:42][CH3:43])[CH:30]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 67436599HCID 67436599, compound

Product 1

HCID 10175276HCID 10175276, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of the title D compound, (R)-1-{4-[3-(4-phenoxy-2-propyl-phenoxy)-propoxy]-benzenesulfonyl}-2,3-dihydro-1H-indole-2-carboxylic acid methyl ester (1.47 g, 2.44 mmol) in methanol (50 mL) under nitrogen at room temperature is added 1N aqueous sodium hydroxide (4.9 mL, 4.9 mmol) dropwise. Upon complete addition, the mixture is stirred at room temperature for 45 minutes, at which time 5 mL of tetrahydrofuran is added to facilitate the dissolution of the starting material. The mixture is stirred overnight. The reaction mixture is concentrated in vacuo, the residue is partitioned between water (50 mL) and ether (50 mL). The aqueous layer is separated and acidified with 1N aqueous hydrochloric acid. The product is extracted into dichloromethane. The extract is washed with brine, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give 1.02 g of (R)-1-{4-[3-(4-phenoxy-2-propyl-phenoxy)-propoxy]-benzenesulfonyl}-2,3-dihydro-1H-indole-2-carboxylic acid as a white foamy solid. The solid is treated with ethanol (1 mL) which results in dissolution of the solid and upon standing crystals start to form. The crystals are separated and dried at high vacuum at 40° C. to give 0.85 g of pure (R)-1-{4-[3-(4-phenoxy-2-propyl-phenoxy)-propoxy]-benzenesulfonyl}-2,3-dihydro-1H-indole-2-carboxylic acid: [M+1]+=588.46, [M−1]−=586.41.

Workup

  1. additionUpon complete addition
  2. additionis added
  3. dissolutionthe dissolution of the starting material
  4. concentrationThe reaction mixture is concentrated in vacuo
  5. customthe residue is partitioned between water (50 mL) and ether (50 mL)
  6. customThe aqueous layer is separated
  7. extractionThe product is extracted into dichloromethane
  8. washThe extract is washed with brine
  9. dry with materialdried over anhydrous sodium sulfate (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-daa498d3a113437fae3d5dd266ff9444
Source dataset
uspto-grants-2007_02
Patent number
US07183304B2

Reaction notes

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