tert-Butyl mercaptan → 3-[1-(4-Bromo-benzyl)-3-tert-butylsulfanyl-5-hydroxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester

HRID 1620807Notes

Reaction equation

HRID 1620807 reaction equation
[CH2:1]([O:3][C:4](=[O:33])[C:5]([CH3:32])([CH3:31])[CH2:6][C:7]1[N:8]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][CH:25]=2)[C:9]2[C:14]([C:15]=1[S:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][C:12]([O:21]C)=[CH:11][CH:10]=2)[CH3:2].CC(S)(C)C.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[CH2:1]([O:3][C:4](=[O:33])[C:5]([CH3:32])([CH3:31])[CH2:6][C:7]1[N:8]([CH2:23][C:24]2[CH:25]=[CH:26][C:27]([Br:30])=[CH:28][CH:29]=2)[C:9]2[C:14]([C:15]=1[S:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][C:12]([OH:21])=[CH:11][CH:10]=2)[CH3:2]

Participants

5

Reactant 3

HCID 6387tert-Butyl mercaptanHCID 6451240Aluminum(III) ChlorideHCID 44474264HCID 44474264, compound

Product 1

HCID 444742653-[1-(4-Bromo-benzyl)-3-tert-butylsulfanyl-5-hydroxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-2.5 °C

Procedure

To a reaction vessel containing dichloromethane (3.3-fold, V/W of starting material) was added 3-[1-(4-bromo-benzyl)-3-tert-butylsulfanyl-5-methoxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester (1.0 eq) under nitrogen. 2-Methyl-2-propanethiol (7.80 eq) was added to the mixture, and the reaction was cooled to a temperature of −5-0° C. While maintaining the reaction mixture at less than 0° C., aluminum chloride (3.30 eq) was added portion-wise, and the reaction was stirred at 0-5° C. for 2 hours. Once no starting material was seen by tlc analysis (5% ethyl acetate/hexanes), the reaction was warmed to room temperature and quenched with ice-water (6.5-fold, V/W of starting material). The mixture was acidified to pH 2 with aqueous 2.0M hydrochloric acid, and the organic layer was separated. The aqueous layer was extracted with dichlormethane to recover remaining product, and the combined organic layers were washed successively with aqueous 1.0M hydrochloric acid, water, and brine, and concentrated in vacuo. Ethyl acetate (1.0-fold, V/W of starting material) was added to the crude material, and the mixture was heated until all the product was in solution. The flask was gradually cooled to 0-2° C., and hexane (11.0-fold, V/W of starting material) was slowly added. The mixture was agitated for 2 hours, and the precipitate was isolated by filtration and dried under vacuum to give the desired product.

Workup

  1. temperatureWhile maintaining the reaction mixture at less than 0° C.
  2. temperaturethe reaction was warmed to room temperature
  3. customquenched with ice-water (6.5-fold, V/W of starting material)
  4. customthe organic layer was separated
  5. extractionThe aqueous layer was extracted with dichlormethane
  6. customto recover
  7. washthe combined organic layers were washed successively with aqueous 1.0M hydrochloric acid, water, and brine
  8. concentrationconcentrated in vacuo
  9. additionEthyl acetate (1.0-fold, V/W of starting material) was added to the crude material
  10. temperaturethe mixture was heated until all the product
  11. temperatureThe flask was gradually cooled to 0-2° C.
  12. additionhexane (11.0-fold, V/W of starting material) was slowly added
  13. stirringThe mixture was agitated for 2 hours
  14. customthe precipitate was isolated by filtration
  15. customdried under vacuum

Sources & evidence

ORD record
ord-3e7fb58cef6a47f6a0bf19cdc3b459cb
Source dataset
uspto-grants-2014_07
Patent number
US08772495B2

Reaction notes

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