Acetic acid, azido-, ethyl ester → ethyl 5-bromo-6-methoxy-1H-indole-2-carboxylate

HRID 400729Notes

Reaction equation

CC[O-].[Na+].[Br:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH:9]=O.[N:16]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[N+]=[N-]>CCO>[Br:5][C:6]1[CH:7]=[C:8]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[NH:16][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:9]2

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of sodium ethylate in ethanol (prepared from sodium (1.92 g; 83.70 mmol) and EtOH (40 mL)) was added dropwise to a cold (−10° C.) solution of 3-bromo-p-anisaldehyde (4 g; 18.60 mmol) and ethyl azidoacetate (ABCR, 27.80 ml; 46.50 mmol) in EtOH (60 mL). After the end of the addition, the reaction mixture was warmed up to 0° C. and stirred at RT for 5 hours. The heterogenous mixture was poured onto ice and stirred for 30 minutes. The solid was collected by filtration and dried under high vacuum. The solid was taken up in xylenes (60 mL) and heated to reflux for 3 hours. The solvent was evaporated and the residue was purified by silica column chromatography (c-Hexane/ethyl acetate, 80/20) to give the title compound as a pale yellow solid. 1H NMR (DMSO-d6) δ 11.87 (s, 1H), 7.89 (s, 1H), 7.05 (s, 1H), 6.98 (s, 1H), 4.31 (q, J=7 Hz, 2H), 3.85 (s, 3H), 1.32 (t, J=7 Hz, 3H). HPLC (Method A), Rt 4.28 min (Purity: 98.1%). LC/MS (Method B): 297.2 (M+H)+.

Workup

additionAfter the end of the addition
additionThe heterogenous mixture was poured onto ice
stirringstirred for 30 minutes
filtrationThe solid was collected by filtration
customdried under high vacuum
temperatureheated
temperatureto reflux for 3 hours
customThe solvent was evaporated
customthe residue was purified by silica column chromatography (c-Hexane/ethyl acetate, 80/20)

Sources & evidence

ORD record: ord-31cfe72e145c442c9af98cb8cdb4e709
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08741923B2

Reaction notes

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