2-(Bromomethyl)acrylic acid ethyl ester → Ethyl 2-(6-fluoro-3-methoxy-2-nitrobenzyl)acrylate

HRID 522512Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.[Li+].[Cl-].Br[CH2:16][C:17](=[CH2:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19].C([Cu])#N>C1COCC1>[F:1][C:2]1[C:3]([CH2:23][C:17](=[CH2:16])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:4]([N+:10]([O-:12])=[O:11])[C:5]([O:8][CH3:9])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -50 °C

Procedure

4-Fluoro-1-methoxy-2-nitrobenzene (21) (171 mg, 1.0 mmol) in THF (2 mL) was added to a solution of TMPZnCl.LiCl (2) (1.3 M in THF, 0.85 mL, 1.1 mmol) at 25° C. and the reaction mixture was then stirred at this temperature for 6 h according to TP 2. After cooling down to −50 ° C., ethyl 2-(bromomethyl)acrylate (230 mg, 1.2 mmol) and CuCN.2LiCl (1.0 M solution in THF, 5 drops) were added at −40° C. and the resulting mixture was stirred at the same temperature for 1 h. The reaction mixture was quenched with a sat. aq. NH4Cl solution (20 mL), extracted with diethyl ether (3×50 mL) and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. Purification by flash-chromatography (CH2Cl2/n-pentane, 1:3) furnished compound 23 (189 mg, 67%) as a colourless oil.

Workup

customThe reaction mixture was quenched with a sat. aq. NH4Cl solution (20 mL)
extractionextracted with diethyl ether (3×50 mL)
dry with materialdried over anhydrous Na2SO4
filtrationAfter filtration
customthe solvent was evaporated in vacuo
customPurification by flash-chromatography (CH2Cl2/n-pentane, 1:3)

Sources & evidence

ORD record: ord-4d68d42b1aab4af2919ea0fd7e859ed1
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334237B2

Reaction notes

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