Ethanol → (6-Bromo-5-fluoro-1-methyl-1H-indol-3-yl)-oxo-acetic acid ethyl ester

HRID 222472Notes

Reaction equation

[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH3:11])=[CH:4][C:3]=1[F:12].[C:13](Cl)(=[O:17])[C:14](Cl)=[O:15].ClCCl.[CH3:22][CH2:23][OH:24]>CCOCC.CCOC(C)=O>[CH2:23]([O:24][C:13](=[O:17])[C:14]([C:6]1[C:5]2[C:9](=[CH:10][C:2]([Br:1])=[C:3]([F:12])[CH:4]=2)[N:8]([CH3:11])[CH:7]=1)=[O:15])[CH3:22]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 6-bromo-5-fluoro-1-methyl-1H-indol (0.23 g, 1.00 mmol) in Et2O (15.0 mL) cooled to 0° C. a 2.0 M solution of oxalyl chloride in dichloromethane (0.56 mL, 5.00 mmol) was added dropwise. The reaction was stirred for 0.5 h at 0° C. and allowed to warm to room temperature and stirred overnight. The mixture was cooled to −20° C. and dry EtOH (2 mL) was added. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography (ethyl acetate-hexane, 1:3) to give the product (0.21 g, 59%). 1H NMR (CDCl3, 300 MHz,): 1.43 (t, J=7.2 Hz, 3H), 3.82 (s, 3H), 4.40 (t, J=7.2 Hz, 2H), 7.47 (d, J=5.4 Hz, 1H), 8.08 (d, J=9.0 Hz, 1H), 8.30 (s, 1H).

Workup

additionwas added dropwise
temperatureto warm to room temperature
stirringstirred overnight
temperatureThe mixture was cooled to −20° C.
washwashed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe residue was purified by column chromatography (ethyl acetate-hexane, 1:3)

Sources & evidence

ORD record: ord-89f956f6a09b479396fb2ac55250b04a
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207216B2

Reaction notes

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