Triethylamine → 5-((E)-2-Ethoxycarbonyl-vinyl)-1H-indole-2-carboxylic acid

HRID 2276997Notes

Reaction equation

HRID 2276997 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=[O:12])=[CH:5]2.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.[C:36]([O:40][CH2:41][CH3:42])(=[O:39])[CH:37]=[CH2:38].CCN(CC)CC>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O.C(#N)C>[CH2:41]([O:40][C:36](/[CH:37]=[CH:38]/[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=[O:12])=[CH:5]2)=[O:39])[CH3:42]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 2521375-Bromo-1H-indole-2-carboxylic acid

Product 1

HCID 579716455-((E)-2-Ethoxycarbonyl-vinyl)-1H-indole-2-carboxylic acidYield 86%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Bromoindole-2-carboxylic acid (400 mg, 1.66 mmol) and tri-O-tolylphosphine (96 mg, 0.32 mmol) were added to a microwave tube. Ethyl acrylate (0.56 ml, 5.6 mmol), Et3N (0.92 ml, 6.6 mmol), acetonitrile (2.5 ml) and Pd(OAc)2 (40 mg, 0.18 mmol) were added. The reaction was placed in a CEM microwave at 150 W, 90° C. for 30 minutes with 5 min ramp time. EtOAc was added and the reaction mixture filtered through celite. The celite pad was washed with DCM and the combined organic fractions removed to give a yellow solid. The solid was redissolved in DCM and extracted into saturated sodium hydrogen carbonate. The aqueous layer was washed with DCM and diethyl ether. The aqueous basic layer was acidified with 2M HCl (pH=5) and the product extracted into EtOAc. The solvent was removed to give the required product (370 mg, 86% yield). LCMS purity 86%, m/z 260 [M++H]+

Workup

  1. filtrationthe reaction mixture filtered through celite
  2. washThe celite pad was washed with DCM
  3. customthe combined organic fractions removed
  4. customto give a yellow solid
  5. extractionextracted into saturated sodium hydrogen carbonate
  6. washThe aqueous layer was washed with DCM and diethyl ether
  7. extractionthe product extracted into EtOAc
  8. customThe solvent was removed

Sources & evidence

ORD record
ord-3c26c7c0566b464d95e8408a02b124f6
Source dataset
uspto-grants-2015_09
Patent number
US09133104B2

Reaction notes

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