tert-Butyl mercaptan → 3-(3-(tert-Butylthio)-1-(4-chlorobenzyl)-5-hydroxy-1H-indol-2-yl)-2,2-dimethylpropanoic acid

HRID 1032977Notes

Reaction equation

HRID 1032977 reaction equation
[H-].[Li+].CN(P(N(C)C)(N(C)C)=O)C.CC(S)(C)C.C[O:20][C:21](=[O:50])[C:22]([CH3:49])([CH3:48])[CH2:23][C:24]1[N:25]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=2)[C:26]2[C:31]([C:32]=1[S:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:30][C:29]([O:38]C)=[CH:28][CH:27]=2>CN(C=O)C>[Cl:47][C:44]1[CH:43]=[CH:42][C:41]([CH2:40][N:25]2[C:26]3[C:31](=[CH:30][C:29]([OH:38])=[CH:28][CH:27]=3)[C:32]([S:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[C:24]2[CH2:23][C:22]([CH3:49])([CH3:48])[C:21]([OH:50])=[O:20])=[CH:46][CH:45]=1

Participants

6

Reactant 4

HCID 6387tert-Butyl mercaptanHCID 12679HexamethylphosphoramideHCID 62714Lithium hydrideHCID 117625003-[1-(4-Chlorobenzyl)-3-(t-butylthio)-5-methoxyindol-2-yl]-2,2-dimethylpropanoic acid methyl ester

Product 1

HCID 200932013-(3-(tert-Butylthio)-1-(4-chlorobenzyl)-5-hydroxy-1H-indol-2-yl)-2,2-dimethylpropanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of LiH (12.6 g) and HMPA (105 mi) in DMF (1050 mi) at 0° C. was added 2-methyl-2-propanethiol (178 mi). The mixture was stirred at room temperature for 30 min, then 3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-methoxyindol-2-yl]-2,2-dimethylpropanoic acid methyl ester (150 g) (EP 419,049, Example 1, Step A) in DMF (450 mi) was added slowly. The mixture was slowly heated to 150° C. and kept at that temperature for 18 hours. After cooling to room temperature, the supernatant layer was decanted and the residue dissolved in H2O and acidifed with 1N HCl, extracted twice with Et2O, washed twice with brine, dried over MgSO4, filtered and evaporated to dryness to provide the title compound.

Workup

  1. temperatureThe mixture was slowly heated to 150° C.
  2. waitkept at that temperature for 18 hours
  3. temperatureAfter cooling to room temperature
  4. customthe supernatant layer was decanted
  5. dissolutionthe residue dissolved in H2O
  6. extractionacidifed with 1N HCl, extracted twice with Et2O
  7. washwashed twice with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-210a53d70f93493b9ba1f5dd64d2c8c8
Source dataset
uspto-grants-1994_05
Patent number
US05308850

Reaction notes

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