Ethyl Acetate → methyl 2-(5-cyano-1H-indol-3-yl)acetate

HRID 1819684Notes

Reaction equation

HRID 1819684 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([O:14][CH3:15])=[O:13].[Cu][C:17]#[N:18].CCOC(C)=O>CN1C(=O)CCC1>[C:17]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([O:14][CH3:15])=[O:13])#[N:18]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 49782545methyl 2-(5-bromo-1H-indol-3-yl)acetateHCID 178418546HCID 178418546, compound2×

Product 1

HCID 18800597methyl 2-(5-cyano-1H-indol-3-yl)acetateYield 47%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Step H (2): To a solution of methyl 2-(5-bromo-1H-indol-3-yl)acetate (134 mg, 0.5 mmol) in NMP (1.0 mL) was added copper(I) cyanide (54 mg, 0.6 mmol). The reaction mixture was microwaved at 180° C. for 1.5 h. More copper (I) cyanide (54 mg, 0.6 mmol) was added, and the mixture was microwaved again at 180° C. for 2 h. 100 mL of EtOAc was added, and the reaction mixture was washed with 1.0 N HCl and H2O. The organic layer was dried and the residue was purified by flash chromatography to give 50 mg of the methyl 2-(5-cyano-1H-indol-3-yl)acetate (yield 47%). MS (ESI) (M+H)+=215.16. 1H NMR (500 MHz, CDCl3) δ ppm 3.73 (s, 3 H) 3.77 (s, 2 H) 7.26 (d, J=2.14 Hz, 1 H) 7.37 (d, J=8.24 Hz, 1 H) 7.40 (dd, J=8.24, 1.22 Hz, 1 H) 7.95 (s, 1 H) 8.54 (s, 1 H).

Workup

  1. customThe reaction mixture was microwaved at 180° C. for 1.5 h
  2. customthe mixture was microwaved again at 180° C. for 2 h
  3. washthe reaction mixture was washed with 1.0 N HCl and H2O
  4. customThe organic layer was dried
  5. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-5911b148f33d4f60b2b3737730459993
Source dataset
uspto-grants-2009_10
Patent number
US07601751B2

Reaction notes

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