Chlorodifluoromethane → (E)-2-(fluoromethylene)-4-(p-fluorophenyl)butan-1-ol

Participants

Reaction Steps

Cool a tetrahydrofuran solution of sodium bis(trimethylsilyl)amide (545 kg, 2M, 877 mol) to -10° C. Slowly add, t-butyl 4-(p-fluorophenyl)butyrate (84.1 kg, 80% by weight in toluene, 353 mol). After 15 minutes, slowly add ethyl chloroformate (38.6 kg, 356 mol) at such a rate that the reaction temperature is maintained at or below -5° C. After 20 minutes, warm the reaction mixture to 40° C.-45° C. Seal the reaction vessel and add chlorodifluoromethane (38.15 kg, 445 mol) to the head space. After 1 hour, cool to 15° C.-20° C. and vent the reaction vessel. Add a solution of acetic acid (421 kg, 20% in water) and stir. After 30 minutes, separate the aqueous layer and evaporate the organic layer in vacuo to obtain a residue. Add toluene (45 kg) and evaporate in vacuo until the internal temperature of the reaction vessel is 55° C. to obtain the title compound as a toluene solution.

Provenance & Evidence