N-bromobutanimide → 4-Bromo-3-(2,5-difluoro-phenoxy)-but-2-enoic acid ethyl ester

HRID 19079Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:17])[CH:5]=[C:6]([O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[F:16])[CH3:7])[CH3:2].[Br:18]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:17])[CH:5]=[C:6]([O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[F:16])[CH2:7][Br:18])[CH3:2]

Participants

Conditions

Temperature: 105 °C

Procedure

A solution of 3-(2,5-difluoro-phenoxy)-but-2-enoic acid ethyl ester (1.35 g, 5.57 mmol) in carbon tetrachloride (30.9 mL) was treated with N-bromosuccinimide (1.09 g, 6.13 mmol) and benzoyl peroxide (108 mg, 0.44 mmol). The reaction was then heated to reflux (105° C.) for 5 h. At this time, the reaction was cooled to 25° C. and then was placed in the refrigerator overnight. At this time, the reaction was removed from the refrigerator. The resulting precipitate was removed by filtration and was rinsed with carbon tetrachloride (25 mL). The filtrate was concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 2% ethyl acetate/hexanes) afforded impure 4-bromo-3-(2,5-difluoro-phenoxy)-but-2-enoic acid ethyl ester (1.56 g, 87%) as a clear oil. The material was used without further purification.

Workup

temperatureThe reaction was then heated
temperatureAt this time, the reaction was cooled to 25° C.
customwas placed in the refrigerator overnight
customAt this time, the reaction was removed from the refrigerator
customThe resulting precipitate was removed by filtration
washwas rinsed with carbon tetrachloride (25 mL)
concentrationThe filtrate was concentrated in vacuo
customPurification by Analogix flash chromatography (40 g, 2% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-f407e707b4034d58ae62bdb2bc1acf35
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741327B2

Reaction notes

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