반응 #61883

반응 방정식

malonate

pyridine

p,p′-difluorobenzophenone

→

diethyl malonate

용매

dichloromethane

THF

THF

THF

반응 조건

후처리

1. 1
   workup.STIRRINGThe ensuing mixture was stirred for 4 days
2. 2
   기타The reaction was quenched with water and diethyl ether
3. 3
   기타The aqueous phase was separated
4. 4
   추출extracted twice more with diethyl ether
5. 5
   세척The combined organic phases were washed with brine, sat. sodium bicarbonate solution and again with brine
6. 6
   건조Drying of the organic phase (MgSO4), filtration and concentration

실험 절차

To THF (80 ml) were added sequentially, a 1.0 M solution of TiCl4 in dichloromethane (80 ml), p,p′-difluorobenzophenone (8.73 g) and diethtyl malonate (6.4 g) in THF 20 ml. After stirring at 0° C. for 40 min, a solution of pyridine (12.8 ml) in THF (28 ml) was added dropwise. The ensuing mixture was stirred for 4 days. The reaction was quenched with water and diethyl ether. The aqueous phase was separated and extracted twice more with diethyl ether. The combined organic phases were washed with brine, sat. sodium bicarbonate solution and again with brine. Drying of the organic phase (MgSO4), filtration and concentration afforded a residue from which residual diethyl malonate was removed by Kugelrohr destillation. The residue was flash chromatographed to provide 1,1-di-p-fluorophenyl-2,2-di-ethoxycarbonylethylene (25%, m.p.=117-119° C.). To this product (5.9 g) were added ammonium chloride (1.31 g), KCN (2.18 g), DMF (175 ml) and water (22 ml) and the mixture was heated to 100° C. for 8 hrs. The cooled reaction mixture was poured into water and extracted (3×) with ethyl ether. The combined organic phases were washed with water, aq. 2N HCl, aq. 5% NaHCO3 and brine. Drying (Na2SO4), filtration and evaporation of volatiles gave a residue which was recrystallised from ether-hexane to afford the title compound (56%; M.p. 90-91° C.).

출처