Reacción #1951056

Ecuación de reacción

4-fluorobenzyl bromide

trimethyl phosphite

→

(4-fluoro-benzyl)-phosphonic acid dimethyl ester

Rendimiento 67.5%

Disolventes

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroat 90° C.
2. 2
   Otroovernight
3. 3
   Temperaturato cool to ambient temperature
4. 4
   LavadoThe solution was washed with saturated sodium bicarbonate (350 mL)
5. 5
   SecadoThe organic phase was dried with magnesium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated by rotatry evaporation
8. 8
   OtroThe resulting crude product was purified by flash silica chromatrography

Procedimiento

4-fluorobenzyl bromide (25 mL, 0.20 mol) was added to a stirred solution of trimethyl phosphite (35.9 mL, 0.30 mol) at ambient temperature, under a nitrogen atmosphere. The resulting solution was heated at 110° C. for six hours, and then at 90° C. overnight. The reaction mixture was allowed to cool to ambient temperature and then ethyl acetate (350 mL) was added. The solution was washed with saturated sodium bicarbonate (350 mL) and then with saturated brine (2×350 mL). The organic phase was dried with magnesium sulfate, filtered, and concentrated by rotatry evaporation. The resulting crude product was purified by flash silica chromatrography using 0-35% acetonitrile in ethyl acetate as eluant to yield (4-fluoro-benzyl)-phosphonic acid dimethyl ester (29.44 g, 135 mmol, 66% yield) as a colorless oil. 1H NMR (400 MHz, DMSO) δ 7.33-7.28 (m, 2H); 7.17-7.12 (dd, 2H); 3.61-3.58 (d, 6H); 3.31-3.24 (d, 2H); ESMS (m/z): (M+1)+ found, 219.

Fuente