Trifluoroacetic acid → ethyl 2-(2-(acetylthio)-1H-indol-3-yl)acetate

HRID 1471640Notes

Reaction equation

HRID 1471640 reaction equation
Br[C:2]1[N:3](C(OC(C)(C)C)=O)[C:4]2[C:9]([C:10]=1[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][CH:7]=[CH:6][CH:5]=2.[C:24](=[S:27])([O-:26])[CH3:25].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:24]([S:27][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][CH:7]=[CH:6][CH:5]=2)(=[O:26])[CH3:25]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23670855Potassium ethanethioateHCID 90281421tert-butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate

Product 1

HCID 90281395ethyl 2-(2-(acetylthio)-1H-indol-3-yl)acetateYield 53.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate (500 mg, 1.3 mmol), potassium ethanethioate (200 mg, 1.7 mmol), tris(dibenzylideneacetone)dipalladium(0) (60 mg, 0.065 mmol), xantphos (75 mg, 0.13 mmol) and DIPEA (0.5 ml, 2.6 mmol) in 1,4-dioxane (4 ml), was heated at 150° C. for 20 minutes in a microwave reactor. TFA (5 ml) was added to the mixture and stirred for 1 hour until Boc deprotection was complete. Filtered reaction mixture through celite and washed with EtOAc (2×50 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was introduced to a silica gel loading column and purified by column chromatography (10-30% EtOAc/Hexanes) to provide the desired product (190 mg, 0.69 mmol), 52.8%. MS (m/z) 278 [M+H]+.

Workup

  1. filtrationFiltered
  2. customreaction mixture through celite
  3. washwashed with EtOAc (2×50 ml)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionThe crude product was introduced to a silica gel loading column
  8. custompurified by column chromatography (10-30% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-7763328454d1409982d0d39c4207dd09
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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