Methyl Acrylate → 3-[3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl]-acrylic acid methyl ester

HRID 1072599Notes

Reaction equation

HRID 1072599 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:30]([O:34][CH3:35])(=[O:33])[CH:31]=[CH2:32].C(N(CC)CC)C.C(OCC)(=O)C>CN(C)C=O.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:35][O:34][C:30](=[O:33])[CH:31]=[CH:32][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:14]=1[NH:13][CH:12]=[C:11]2[CH2:10][C:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])([CH3:29])[CH3:28]

Participants

8

Reactant 4

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 86595245trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester

Product 1

HCID 695178463-[3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl]-acrylic acid methyl esterYield 82%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

Trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester (200 mg, 0.46 mmol), methyl acrylate (80 mg, 0.92 mmol) and triethylamine (0.40 mL, 3.0 mmol) is stirred in dimethylformamide (2.0 mL) at room temperature for 30 minutes. Dichlorobis(triphenylphosphine)palladium (31 mg, 0.045 mmol) is added, the reaction mixture is heated to 90° C. and allowed to stir overnight. The reaction is cooled to room temperature, poured into a separatory funnel containing ethyl acetate and brine (50 mL each) and the aqeous layer is extracted with ethyl acetate (50 mL). The combined organic layers are washed with brine, dried (Na2SO4) and evaporated. The residue is purified using silica gel chromatography (20% ethyl acetate/hexane) to give 140 mg of 3-[3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl]-acrylic acid methyl ester (82%). FDMS m/e=372.2 (M++1). The title compound is prepared from 3-[3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl]-acrylic acid methyl ester as described for the alternate preparation of Amine 6 (82%). FDMS m/e=277.2 (M++1).

Workup

  1. temperatureThe reaction is cooled to room temperature
  2. additionpoured into a separatory funnel
  3. extractionthe aqeous layer is extracted with ethyl acetate (50 mL)
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe residue is purified

Sources & evidence

ORD record
ord-8fb905c3d58e40b59229f0daf7baf130
Source dataset
uspto-grants-2005_06
Patent number
US06911463B2

Reaction notes

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