반응 #417809

반응 방정식

4,4'-difluorobenzophenone

ethyl cyanoacetate

benzene

β-alanine

→

pure title compound

수율 56.3%

Ethyl 2-cyano-3,3-bis(4-fluorophenyl)-2-propenoate

수율 56.3%

용매

acetic acid

water

water

반응 조건

후처리

1. 1
   기타Separation of water
2. 2
   기타was rapid during the first 2 hours (0.4 mL aqueous layer collected)
3. 3
   workup.DISTILLATIONAzeotropic distillation
4. 4
   세척Analytical TLC eluted with 10% EtOAc in hexanes (v/v) (Merck plate, 0.25 mm Silica gel-F)
5. 5
   기타Crude reaction mixture
6. 6
   세척was washed with water (40 mL×2)
7. 7
   추출the combined aqueous washes were extracted with EtOAc (150 mL×2)
8. 8
   건조dried over MgSO4
9. 9
   농축concentrated under reduced pressure
10. 10
    기타to crystallize the product as pale cubic crystals
11. 11
    기타The crude product was collected
12. 12
    세척washed with 1:1 EtOAc in hexanes (v/v)
13. 13
    기타then recrystallized from 8:1 (hexanes:ethyl acetate v/v)

실험 절차

A mixture of 20.0 g (92 mmoles) of 4,4'-difluorobenzophenone, 11.0 g (97 mmoles) of ethyl cyanoacetate in a mixed solvent of 100 mL of dry benzene and 20 mL of glacial acetic acid containing a catalytic amount of β-alanine (0.9 g) was refluxed with separation of water using a Dean-Stark water trap. Separation of water was rapid during the first 2 hours (0.4 mL aqueous layer collected) but slower afterward. Azeotropic distillation was continued for a period of 14 days. Analytical TLC eluted with 10% EtOAc in hexanes (v/v) (Merck plate, 0.25 mm Silica gel-F) showed two spots at Rf =0.2 (desired product) and at Rf =0.45 (4,4'-difluorobenzophenone starting material). Crude reaction mixture was washed with water (40 mL×2), and the combined aqueous washes were extracted with EtOAc (150 mL×2). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure to crystallize the product as pale cubic crystals. The crude product was collected, washed with 1:1 EtOAc in hexanes (v/v) then recrystallized from 8:1 (hexanes:ethyl acetate v/v) to give 16.2 g (56.3%) of analytical pure title compound; m.p.=114°-116° C.

출처