Acetic Anhydride → 3-(Acetyloxy)-4-methyl-2-methylenepentanenitrile

Participants

Reaction Conditions

Reaction Steps

To a 500 mL, four-necked, round-bottom flask equipped with an overhead stirrer, a temperature probe, a reflux condenser, and a nitrogen inlet is charged acetic anhydride (40 mL, 0.45 mol). This solution is heated to 50° C. and a solution of 3-hydroxy-4-methyl-2-methylenepentanenitrile (50 g, 0.40 mol) and 4-(dimethylamino)pyridine (1.5 g) in tetrahydrofuran (25 mL) is added over 35 minutes. A temperature of 50° C. to 63° C. is maintained without external heating. After the addition is complete, the reaction mixture is heated at 60° C. for 75 minutes. The solution is cooled to 30° C. and the cooled reaction mixture is diluted with 30 mL of tert-butylmethyl ether (MTBE) and 25 mL of water. This mixture is cooled to 10° C. and a solution of 50% aqueous sodium hydroxide (37 g, 0.46 mol) diluted with 45 mL of water is added with cooling, such that the temperature is maintained at about 15° C. For the final pH adjustment, 50% aqueous sodium hydroxide 9.8 g (0.12 mol) is added dropwise to a final pH of 9.4. After adding 10 mL of water and 10 to 15 mL of MTBE, the reaction mixture is phased and separated. The upper organic product layer is separated and washed with 25 mL of brine, dried over magnesium sulfate, and concentrated in vacuo to provide 63.7 g (95%) of acetic acid 2-cyano-1-isopropyl-allyl ester as a pale yellow oil. Ethyl 3-cyano-5-methyl hex-3-enoate

Provenance & Evidence