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 2366093Notes

Reaction equation

HRID 2366093 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.[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl>[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 CH2Cl2 (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). 2-Methyl-2-propanethiol (7.80 eq) was subsequently added to the reaction mixture and the reaction was cooled down to a temperature of −5 to 0° C. While maintaining the reaction mixture at this temperature, AlCl3 (3.30 eq) was added portion-wise to the reaction. The reaction was stirred at a temperature of 0 to 5° C. for about 2 hours, then subsequently warmed to 20-25° C. The reaction was then quenched with water (6.5 fold; v/w of starting material) and the mixture acidified to a pH of 2 with 2.0M HCl. The organic layer was then collected and the aqueous layer washed with CH2Cl2 to recover remaining product. The organic layers were combined and washed with 1.0M HCl and water followed by a brine wash and concentrated in vacuo. Ethyl acetate (1.0 fold; v/w of starting material) was added to the solid and heated to dissolve the product. The flask was gradually cooled to 0-2° C. followed by the slow addition of hexanes. The mixture was agitated for a period of about 2 hours, followed by filtration to collect the solid. The solid was subsequently dried under vacuum.

Workup

  1. additionwas added portion-wise
  2. customto the reaction
  3. temperaturesubsequently warmed to 20-25° C
  4. customThe reaction was then quenched with water (6.5 fold; v/w of starting material)
  5. customThe organic layer was then collected
  6. washthe aqueous layer washed with CH2Cl2
  7. customto recover
  8. washwashed with 1.0M HCl and water
  9. washwash
  10. concentrationconcentrated in vacuo
  11. additionEthyl acetate (1.0 fold; v/w of starting material) was added to the solid
  12. temperatureheated
  13. dissolutionto dissolve the product
  14. temperatureThe flask was gradually cooled to 0-2° C.
  15. additionfollowed by the slow addition of hexanes
  16. stirringThe mixture was agitated for a period of about 2 hours
  17. filtrationfollowed by filtration
  18. customto collect the solid
  19. customThe solid was subsequently dried under vacuum

Sources & evidence

ORD record
ord-c57ced7eb7064a189faae109333df557
Source dataset
uspto-grants-2014_04
Patent number
US08697730B2

Reaction notes

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