Triethylamine → [1,1-dimethyl-2-(7-thiophen-3-yl-1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester

HRID 8093

Reaction equation

HRID 8093 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:29])([CH3:28])[CH2:10][C:11]1[C:19]2[C:14](=[C:15](OS(C(F)(F)F)(=O)=O)[CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[S:37]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38]1>CN(C)C=O.[Cl-].[Na+].O.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:29])([CH3:28])[CH2:10][C:11]1[C:19]2[C:14](=[C:15]([C:39]3[CH:40]=[CH:41][S:37][CH:38]=3)[CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 581760Thiophene-3-boronic acidHCID 86595245trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester

Product 1

HCID 69516995[1,1-dimethyl-2-(7-thiophen-3-yl-1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl esterYield 69%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester (340 mg, 0.779 mmol) in dimethylformamide (5 mL) is added triethylamine (0.14 mL, 1.01 mmol), tetrakis(triphenylphosphine)-palladium (36 mg, 0.0312 mmol) and 3-thiopheneboronic acid (130 mg, 1.01 mmol). The mixture is refluxed for. 22 hours, then cooled and diluted with brine and ethyl acetate. The organic phase is washed 7 times with brine. The organics are dried over anhydrous sodium sulfate, filtered and then evaporated in vacuo. The residue is purified using silica gel chromatography (hexane/20% ethyl acetate, hexane gradient elution) to give 198 mg of [1,1-dimethyl-2-(7-thiophen-3-yl-1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester (69%). FDMS m/e=371 (M++1).

Workup

  1. temperatureThe mixture is refluxed for
  2. temperature22 hours, then cooled
  3. washThe organic phase is washed 7 times with brine
  4. dry with materialThe organics are dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue is purified
  8. washsilica gel chromatography (hexane/20% ethyl acetate, hexane gradient elution)

Sources & evidence

ORD record
ord-61c1e1a0aa5e442d91a796b5a4f41109
Source dataset
uspto-grants-2006_08
Patent number
US07087635B2

Linked notes

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