Toluene → 3-[(4-Fluorophenyl)methylidene]piperidin-2-one
Reaktionsgleichung
[C:1]1(=[O:7])[NH:6][CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O[C:13](=O)[C:14]([F:17])(F)F)=O.[C:21]1([CH3:27])[CH:26]=CC=[CH:23][CH:22]=1>>[F:17][C:14]1[CH:13]=[CH:26][C:21]([CH:27]=[C:2]2[CH2:3][CH2:4][CH2:5][NH:6][C:1]2=[O:7])=[CH:22][CH:23]=1Komponenten
4
Reaktionsbedingungen
- Temperatur
- 60 °C
Versuchsvorschrift
This example illustrates the preparation of the compound of formula II (n=2, R1=p-fluorophenyl) at a multi-kilogram scale. A 30 gallon (120 L) glass-lined reactor was charged with valerolactam (18.0 kg) and toluene (42.0 kg). Trifluoroacetic anhydride (42.0 kg) was added over 30 min and the mixture was stirred for an additional 60 min. Volatiles were distilled off at 60-70° C. at 140 torr. Toluene (50.0 kg) was added and the mixture was further distilled until approximately 27 L remained in the pot and this process was repeated twice. To the residue was added tert-butanol (18.8 kg) and 4-fluorobenzaldehyde (20.3 kg). The resultant solution was slowly transferred to 100 gallon (400 L) glass-lined reactor containing potassium tert-butoxide in tetrahydrofuran (122 kg of a 20% solution). The mixture was warmed to 60° C. for 1 h. Volatiles were distilled at 40-50° C. at 250 torr to a volume of approximately 100 L. Water (180 L) was added to the slurry at 40° C. and the mixture was cooled to 5° C. for 2 h and collected by filtration. The wet cake was washed and reslurried with water (3×200 L) and dried in a tray dryer (50° C., 50 torr) to afford crude 3-p-fluorobenzylidene-2-piperidone (32.6 kg) whose purity by HPLC was 70.3 wt % (95.4 area %).