反应详情

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.

1. additionSlowly add
2. waitAfter 20 minutes
3. temperaturewarm the reaction mixture to 40° C.-45° C
4. customSeal the reaction vessel
5. waitAfter 1 hour
6. temperaturecool to 15° C.-20° C.
7. waitAfter 30 minutes
8. customseparate the aqueous layer
9. customevaporate the organic layer in vacuo
10. customto obtain a residue
11. customAdd toluene (45 kg) and evaporate in vacuo until the internal temperature of the reaction vessel
12. customis 55° C.