Water → HCID 21254046, compound

HRID 1292409Notes

Reaction equation

HRID 1292409 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]([C:15]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[CH:16]=1)=[C:9]2[CH2:23][CH2:24][N:25]([C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42])[CH2:26][CH2:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][S:37]([CH3:40])(=[O:39])=[O:38])=[CH:32][CH:31]=1)=[O:5])C.[OH-].[K+].O>CO>[CH2:44]([O:43][C:41]([N:25]([CH2:26][CH2:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][S:37]([CH3:40])(=[O:38])=[O:39])=[CH:32][CH:31]=1)[CH2:24][CH2:23][C:9]1[C:8]2[C:12](=[CH:13][CH:14]=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=2)[NH:11][C:10]=1[C:15]1[CH:16]=[C:17]([CH3:22])[CH:18]=[C:19]([CH3:21])[CH:20]=1)=[O:42])[C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 70226131HCID 70226131, compound

Product 1

HCID 21254046HCID 21254046, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 600 mg (0.862 mmol) of 3-(2-{benzyloxycarbonyl-[4-(4-methanesulfonylaminophenyl)butyl]amino}ethyl)-2-(3,5-dimethylphenyl)-1H-indole-5-carboxylic acid ethyl ester in 18 mL (9 mmol) of 0.50N potassium hydroxide in methanol was stirred at about 60° C. as 2.0 mL of water was added gradually. Stirring was continued at 60°-65° C. under nitrogen for 10 hours. The cooled mixture, which contained a white precipitate, was concentrated to small volume in vacuo. The residual suspension was partitioned between 25 mL of ethyl acetate and 25 mL of 0.5N hydrochloric acid. After the aqueous layer was separated, precipitation began in the ethyl acetate phase. Dilution with 25 mL of tetrahydrofuran redissolved the precipitate. The aqueous phase was back-extracted with 10 mL of ethyl acetate+10 mL of tetrahydrofuran. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residual solid was triturated with diethyl ether, collected on a filter, and washed with some additional ether to give (after drying) 573 mg (100%) of a powder, mp 211.5°-213° C.; virtually homogeneous by TLC(92.5:7.5 CH2Cl2 --MeOH). 500 MHz 1H NMR (DMSO-d6) was consistent with the assigned structure. Mass spectrum (ESI): m/e=668 (M+H).

Workup

  1. additionwas added gradually
  2. concentrationwas concentrated to small volume in vacuo
  3. customThe residual suspension was partitioned between 25 mL of ethyl acetate and 25 mL of 0.5N hydrochloric acid
  4. customAfter the aqueous layer was separated
  5. customprecipitation
  6. dissolutionDilution with 25 mL of tetrahydrofuran redissolved the precipitate
  7. extractionThe aqueous phase was back-extracted with 10 mL of ethyl acetate+10 mL of tetrahydrofuran
  8. dry with materialThe combined organic phases were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residual solid was triturated with diethyl ether
  12. customcollected on a filter
  13. washwashed with some additional ether
  14. customto give
  15. dry with material(after drying) 573 mg (100%) of a powder, mp 211.5°-213° C.

Sources & evidence

ORD record
ord-3f23534d2a4e450ba1b0b8f0a506426a
Source dataset
uspto-grants-1998_05
Patent number
US05756507

Reaction notes

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