5-Nitroindole → 3-(4-Cyano-2-methoxybenzyl)-5-nitroindole

HRID 1646363Notes

Reaction equation

[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2)([O-:3])=[O:2].Br[CH2:14][C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[O:23][CH3:24]>O1CCOCC1.[Ag-]=O.[Ag]=O>[C:19]([C:18]1[CH:21]=[CH:22][C:15]([CH2:14][C:7]2[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[NH:9][CH:8]=2)=[C:16]([O:23][CH3:24])[CH:17]=1)#[N:20]

Participants

Conditions

Temperature: 100 °C

Procedure

An efficiently stirred mixture of 5-nitroindole (3.24 g.), bromide (W) (4.57 g.) and silver (I) oxide (4.87 g.) in dry dioxane (90 ml.) was heated at 100° C for 5 hours. Additional silver oxide (2 g.) was added, and heating continued for 1 hour. The cooled mixture was evaporated, the residue diluted with dichloromethane, filtered, washing the filter cake with dichloromethane until the washings were colorless, and the combined filtrate evaporated. The product was purified by flash chromatography on silica gel, eluting with 3:7 v/v ethyl acetate:hexane, giving a product which was crystallized from a mixture of ethyl acetate and hexane to give 3-(4-cyano-2-methoxybenzyl)-5-nitroindole (1.87 g., 30%) as a yellow powder, m.p. 204°-206° C.: partial NMR (80 MHz, DMSO-d6): 3.92 (s,3 H, OMe); 4.12 (s,2 H, ArCH2).

Workup

temperatureheating
customThe cooled mixture was evaporated
additionthe residue diluted with dichloromethane
filtrationfiltered
washwashing the filter cake with dichloromethane until the washings
customthe combined filtrate evaporated
customThe product was purified by flash chromatography on silica gel
washeluting with 3:7 v/v ethyl acetate
customhexane, giving a product which
customwas crystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record: ord-00e53ae318124a65a8f8ae91d6ba69e5
Source dataset: uspto-grants-1993_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05179112

Reaction notes

Loading…