5-Bromo-1-[tert-butyl(dimethyl)silyl]-1H-indole → HCID 59381924, compound

HRID 2354567Notes

Reaction equation

HRID 2354567 reaction equation
CC([O-])(C)C.[Na+].Br[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH:12]=[CH:11]2.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][NH:34][CH:33]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>C1(C)C(C)=CC=CC=1.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][N:34]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH:12]=[CH:11]3)[CH:33]([CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:32]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

8

Reactant 3

HCID 114723735-Bromo-1-[tert-butyl(dimethyl)silyl]-1H-indoleHCID 23676156Sodium t-butoxideHCID 44118664tert-Butyl 3-benzylpiperazine-1-carboxylate

Product 1

HCID 59381924HCID 59381924, compoundYield 74.1%

Reagents, catalysts & solvents 4

HCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 7237O-XyleneSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of Pd(OAc)2 (0.054 g, 0.2 mmol), NaOtBu (0.64 g, 6.6 mmol) in xylene (7.0 mL) in a screw-capped tube was added tBu3P (0.049 g, 0.2 mmol). After 10 minutes a solution of 5-bromo-1-(tert-butyl-dimethyl-silanyl)-1H-indole (1.30 g, 4.4 mmol) in xylene (7.0 mL) and a solution of 3-benzyl-piperazine-1-carboxylic acid tert-butyl ester (1.34 g, 4.8 mmol) in xylene (8.0 mL) were added. The mixture was heated to 80° C. for 30 minutes, then cooled to room temperature. The reaction mixture was taken up in ethyl acetate, filtered through a pad of celite, and concentrated under reduced pressure. Purification via flash chromatography (gradient: 2% to 20% EtOAc in hexane) afforded 3-Benzyl-4-[1-(tert-butyl-dimethyl-silanyl)-1H-indol-5-yl]-piperazine-1-carboxylic acid tert-butyl ester (1.65 g, 74%) as a pale yellow solid; MS (M+H)=506.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through a pad of celite
  3. concentrationconcentrated under reduced pressure
  4. customPurification via flash chromatography (gradient: 2% to 20% EtOAc in hexane)

Sources & evidence

ORD record
ord-826123f264c64f698585ee43f7cf6ce2
Source dataset
uspto-grants-2010_07
Patent number
US07754721B2

Reaction notes

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