Ethyl 2-methylene-3-phenylpropionate

Ethyl 2-methylene-3-phenylpropionate, 80 3-Ethyl-7-methyl-frans,c/r-2,6-nonadiene-l-ol, 295... 

To a 2 L, 3-neck Morton flask fitted with a thermometer, a mechanical stirrer, and an addition funnel was added the methyl 3-hydroxy-2-methylene-3-phenylpropionate (305.9 g, 1.585 mol) followed by addition of 48% HBr (505 ml, 4.46 mol) in one portion. The flask was immersed in an ice-water bath, at which time concentrated sulfuric acid (460 ml, 8.62 mol) was added dropwise over 90 min and the internal temperature of the reaction mixture was maintained at 23°-27°C throughout the addition process. After removal of the ice-water bath, the mixture was allowed to stir at room temperature overnight. The solution was then transferred to a separatory funnel and the organic layer was allowed to separate from the acid layer. The acids were drained and the organic layer was diluted with 2 L of a 1 1 ethyl acetate/hexane solution, washed with saturated aqueous sodium bicarbonate solution (1 L), dried over sodium sulfate, and concentrated to yield 400.0 g (99%) of the desired (Z)-l-bromo-2-carbomethoxy-3-phenyl-2-propene as a light yellow oil, which was used without any additional purification, boiling point 180°C (12 mm). 

Cyano(ethoxycarbonyl)methylene)amino)-N,N,N, N -tetramethyluronium tetrafluo-roborate (1.42 mmol) and N,N-diisopropylethylamine (1.35 mmol) were added successively with ice cooling to a solution of the product from Step 6 (1.42 mmol) and ethyl (S)-3-amino-3-phenylpropionate (1.42 mmol) dissolved in 20 ml DMF. After 1 hour at ambient temperature the solvent was removed and the residue dissolved in EtOAc. The solution was successively washed twice with aqueous solutions of KHSO4, NaHC03, and brine. The organic phase was dried, concentrated, the product isolated by chromatography on silica gel using EtOAc/heptane, 1 1, and the product isolated in 85% yield. 

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