Sodium hydride → 6-chloro-1-(cyano-methyl-methyl)-1H-indole-2-carboxylic acid ethyl ester

HRID 853044Notes

Reaction equation

[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[C:12]([Cl:17])[CH:11]=2)=[O:7])[CH3:4].Br[CH:19]([CH3:22])[C:20]#[N:21]>CN(C)C=O>[CH2:3]([O:5][C:6]([C:8]1[N:9]([CH:19]([C:20]#[N:21])[CH3:22])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[C:12]([Cl:17])[CH:11]=2)=[O:7])[CH3:4]

Participants

Conditions

Temperature: 0 °C

Procedure

Sodiumhydride (0.89 g, 20.1 mmol) was suspended in dimethylformamide (15 mL) and a solution of 6-chloro-1H-indole-2-carboxylic acid ethyl ester (2.00 g, 8.9 mmol) in dimethylformamide (8 mL) was added at 0° C. The mixture was stirred for 1 h at 0° C. then 2-bromo-propionitrile (3.6 g, 23.95 mmol) was added. After 1 h at room temperature the mixture was heated at 75° C. for 18 hours. The reaction mixture was then added to an ice/water mixture (100 mL) and extracted with ethylacetate. The organic phases were pooled washed with brine, dried with Na2SO4 and the solvent was removed in vacuo. Chromatography on silica gel (ether/n-hexane 1:4) yielded 6-chloro-1-(cyano-methyl-methyl)-1H-indole-2-carboxylic acid ethyl ester (2.06 g, 67%) as a colorless solid, MS: m/e=277.2 (M+H+).

Workup

temperatureAfter 1 h at room temperature the mixture was heated at 75° C. for 18 hours
extractionextracted with ethylacetate
washThe organic phases were pooled washed with brine
dry with materialdried with Na2SO4
customthe solvent was removed in vacuo

Sources & evidence

ORD record: ord-51b73faeda354cc4b2ede80b96b61208
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07253281B2

Reaction notes

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