55039-89-9

2,2-Difluoro-4-pentenoic acid is involved in the iodolactonization reaction to give the corresponding gamma- lactone, which is converted to prepare prepare 5-hydroxy-3,3-difluoropiperidine.

The general procedure for synthesizing 2,2-difluoro-4-pentenoic acid from allyl chlorodifluoroacetate is as follows: in Example 9, 100.0 g (0.59 mol) of allyl chlorodifluoroacetate, 42.2 g (0.65 mol) of zinc powder activated by the Fieser and Fieser methods, 96.7 g (0.88 mol) of trimethylchlorosilane and 400 mL of anhydrous acetonitrile were added to a glass autoclave and a trace amount of iodine was added as initiator. The reaction mixture was heated at 100 °C for 48 hours. Upon completion of the reaction, the precipitated zinc salt was removed by filtration and the filtrate was hydrolyzed with water. Subsequently, the reaction mixture was alkalized with 2N NaOH solution. The dark brown aqueous phase was extracted with pentane and then acidified with semi-concentrated hydrochloric acid before the product was extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and concentrated in a rotary evaporator and the residue was vacuum distilled. A final 59.4 g (74% yield) of the colorless oily product 2,2-difluoro-4-pentenoic acid was obtained with a boiling point of 73°-75°C/15.6 mbar.

[1] Chemical Research in Toxicology, 1995, vol. 8, # 5, p. 671 - 682
[2] Patent: US4892962, 1990, A