Reacción #8263

Ecuación de reacción

3-(4-(3(S)-Aminopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyl-oxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride salt

2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl chloride

→

desired product

Rendimiento 143.5%

3-(4-(3(S)-(2(S),3-Dihydroxypropanoyl)pyrrolidin-1-yl)-3-fluorophenyl)-5(S)-(isoxazol-3-ylaminomethyl)oxazolidin-2-one

Rendimiento 143.5%

Disolventes

pyridine

dichloromethane

ethyl acetate

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe organic layer separated
2. 2
   Lavadowashed with aqueous sodium bicarbonate (10 ml) and brine (10 ml)
3. 3
   Otroevaporated
4. 4
   Otroazeotroped with toluene (20 ml)
5. 5
   OtroThe residue was purified by chromatography on a 10 g silica Mega Bond Elut® column
6. 6
   Lavadoeluting with
7. 7
   Temperaturaa gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane
8. 8
   Otroevaporated

Procedimiento

3-(4-(3(S)-Aminopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyl-oxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride salt (400 mg, 0.698 mM) in pyridine (5 ml) was treated dropwise with a solution of 2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl chloride (200 mg, 1.2 mM) in dichloromethane (2 ml), and the mixture stirred 3 hours at ambient temperature. The mixture was diluted with ethyl acetate (15 ml) and water (15 ml), the organic layer separated, washed with aqueous sodium bicarbonate (10 ml) and brine (10 ml), and evaporated, then azeotroped with toluene (20 ml). The residue was purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (435 mg).

Fuente