2,2-Dimethoxypropane → Methyl 3-cyano-2-phenylpropanoate

Participants

Reaction Steps

DL-tropic acid (10 g, 120 mmol), 2,2-dimethoxypropane (12.48 g, 120 mmol) and catalytical amount of p-toluenesulfonic acid (100 mg) were mixed in MeOH (50 ml) and refluxed overnight. The reaction mixture was cooled and concentrated in-vacuo to dryness and then dissolved in ethyl acetate. The organic phase was washed with water, brine and dried with sodium sulfate, and concentrated in-vacuo to dryness. The crude product was dissolved in anhydrous mentylene chloride (150 ml). Triethylamine (7.27 g, 72 mmol) and methanesulfonyl chloride (8.24 g, 72 mmol) were added and stirred at room temperature overnight before it was washed with water, brine and dried with sodium sulfate. The concentrated residue was heated with KCN (5.88 g, 120 mmol) and tetrabutylammonium cyanide (2 g, 7.4 mmol) in DMF at 80° C. for 1 hour. After cooled down to room temperature, reaction mixture was diluted with methylene chloride, washed with water, brine and dried with Na2SO4. After concentration in-vacuo, the crude product was purified by silica flash chromatography (10% ethyl acetate in hexanes) to afford 6.4 g of the desired product as a yellowish solid (58% in three steps). 1H NMR (500 MHz, CDCl3) δ: 7.37 (m, 3 H), 7.27 (m, 2 H), 3.94 (t, J=7.63 Hz, 1 H), 3.73 (s, 3 H), 3.04 (dd, J=16.79, 7.63 Hz, 1 H), 2.81 (dd, J=17.09, 7.63 Hz, 1H).

Provenance & Evidence