N-methyl-2-pyrrolidone → ethyl 5-cyano-6-methoxy-1H-indole-2-carboxylate

HRID 400730Notes

Reaction equation

HRID 400730 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[NH:7][C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:5]2.[CH3:18][N:19]1C(=O)CCC1>>[C:18]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[NH:7][C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:5]2)#[N:19]

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 14916489ethyl 5-bromo-6-methoxy-1H-indole-2-carboxylate

Product 1

HCID 67401331ethyl 5-cyano-6-methoxy-1H-indole-2-carboxylate

Conditions

Temperature
200 °C

Procedure

A mixture of ethyl 5-bromo-6-methoxy-1H-indole-2-carboxylate obtained in step 1 (300 mg; 1.01 mmol) and cuprous cyanide (108 mg; 1.21 mmol) in NMP (10 mL) was heated under microwave irradiations at 200° C. for 30 minutes. The dark solution was filtered through a short pad of silica, which was washed with DCM. The obtained dark red solution was concentrated in vacuo and the oily residue was precipitated in water. The solid was collected by filtration, washed thoroughly with water and dried under high vacuum. Purification by silica column chromatography (DCM then DCM/MeOH, 99/1) gave the title compound as a slightly pink solid. HPLC (Method A), Rt 3.45 min (Purity: 97.4%). LC/MS (Method B): 243.2 (M+H)+.

Workup

  1. filtrationThe dark solution was filtered through a short pad of silica, which
  2. washwas washed with DCM
  3. concentrationThe obtained dark red solution was concentrated in vacuo
  4. customthe oily residue was precipitated in water
  5. filtrationThe solid was collected by filtration
  6. washwashed thoroughly with water
  7. customdried under high vacuum
  8. customPurification by silica column chromatography (DCM

Sources & evidence

ORD record
ord-ff301c68923e4af2aa5f2f58aeb2400e
Source dataset
uspto-grants-2014_06
Patent number
US08741923B2

Reaction notes

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