Reacción #8250

Ecuación de reacción

sodium bicarbonate

5-Benzyloxycarbonylamino-2-(2-methylimidazol-1-yl)fluorobenzene

n-butyllithium

(R)glycidylbutyrate

→

title compound

Rendimiento 44.5%

3-(3-Fluoro-4-(2-methylimidazol-1-yl)phenyl)-5(R)-hydroxymethyloxazolidin-2-one

Rendimiento 44.5%

Disolventes

ethyl acetate

tetrahydrofuran

1,3-dimethyl-2,4,5,6-tetrahydro-2(1H)-pyrimidinone

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooled to −70°
2. 2
   workup.STIRRINGStirring
3. 3
   workup.WAITwas continued for 16 hours
4. 4
   Otrothe organic layer separated
5. 5
   Extracciónthe aqueous extracted with further ethyl acetate (3×750 ml)
6. 6
   SecadoThe combined extracts were dried (magnesium sulfate)
7. 7
   Otroevaporated
8. 8
   Otrothe resulting oil triturated with diethyl ether

Procedimiento

5-Benzyloxycarbonylamino-2-(2-methylimidazol-1-yl)fluorobenzene (54 g, 0.166 M) was dissolved in a mixture of dry tetrahydrofuran (600 ml) and 1,3-dimethyl-2,4,5,6-tetrahydro-2(1H)-pyrimidinone (100 ml) under nitrogen, cooled to −70°, and treated with a solution of n-butyllithium (1.6 M in isohexane, 114 ml), over 30 minutes. After stirring for 30 minutes at −70°, a solution of (R)glycidylbutyrate (26.35 g, 0.183 M) in dry tetrahydrofuran (50 ml) was added over 15 minutes. Stirring was continued for 16 hours allowing the temperature to rise to ambient. The mixture was treated with aqueous sodium bicarbonate (5%, 500 ml) and ethyl acetate (800 ml), the organic layer separated, and the aqueous extracted with further ethyl acetate (3×750 ml). The combined extracts were dried (magnesium sulfate) and evaporated, and the resulting oil triturated with diethyl ether. The resulting solid was recrystallisd from isopropanol to give the title compound (21.5 g).

Fuente