Reacción #64446

Ecuación de reacción

N-Chlorosuccinimide

lithium bis(trimethylsilyl)amide

Acetophenone

ethenylidenebisphosphonic acid tetraethyl ester

→

title compound

[1-Chloro4-oxo4-phenylbutylidene]bisphosphonic acid tetraethyl ester

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooled to -78°
2. 2
   workup.STIRRINGThe solution is stirred for several minutes
3. 3
   Temperaturathen warmed to 0° for 1 hour
4. 4
   workup.STIRRINGthe solution was stirred at 22° for 18 hours
5. 5
   OtroThe reaction is quenched with aqueous ammonium chloride
6. 6
   Concentraciónconcentrated
7. 7
   workup.ADDITIONThe residue is diluted with ethyl acetate
8. 8
   Lavadowashed with sulfuric acid (2N, 2×), water, sodium bicarbonate, saline
9. 9
   Secadodried with magnesium sulfate
10. 10
    Concentraciónconcentrated
11. 11
    OtroThe resultant mixture is chromatographed
12. 12
    Lavadoeluting with ethyl acetate
13. 13
    Temperaturaslowly increased from 1 to 5% ethanol/ethyl acetate
14. 14
    Concentraciónconcentrated

Procedimiento

Acetophenone (1.17 ml) is dissolved in THF (20 ml), cooled to -78° and treated with lithium bis(trimethylsilyl)amide. The solution is stirred for 30 minutes and a solution of ethenylidenebisphosphonic acid tetraethyl ester (I, 2.7g) in THF (5 ml) is added. The solution is stirred for several minutes then warmed to 0° for 1 hour. N-Chlorosuccinimide (1.33 g) is added and the solution was stirred at 22° for 18 hours. The reaction is quenched with aqueous ammonium chloride and concentrated. The residue is diluted with ethyl acetate and washed with sulfuric acid (2N, 2×), water, sodium bicarbonate, saline and dried with magnesium sulfate and concentrated. The resultant mixture is chromatographed eluting with ethyl acetate, slowly increased from 1 to 5% ethanol/ethyl acetate. The appropriate fractions are pooled and concentrated to give the title compound, MS (m/e) 454, 426, 322 and 105; IR (neat) 1686, 1599, 1581, 1448, 1391, 1368, 1259, 1214 and 1163 cm-1 ; NMR (CDCl3) 8.02-7.99, 7.59-7.54, 7.49-7.44, 4.37-4.25, 3.50, 2.78-2.64 and 1.38 δ. Another compound is formed by the reaction which is not within the scope of the invention.

Fuente