Réaction #85622

Équation de réaction

(R)-3-(2,6-dichloropyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one

trimethylsilyldiazomethane

tetrafluoroboric acid

trimethylsilyldiazomethane

DCM

→

(R)-3-(2,6-dichloropyrimidin-4-yl)-4-((R)-1-methoxyethyl)oxazolidin-2-one

Rendement 31.0%

Solvants

EtOAc Heptane

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONadded 20 min apart
2. 2
   workup.ADDITIONadded 20 min
3. 3
   workup.ADDITIONapart was added
4. 4
   AutreReaction mixture
5. 5
   Autrewas quenched with water
6. 6
   workup.ADDITIONdiluted with DCM
7. 7
   Extractionthe aqueous phase extracted with DCM
8. 8
   Lavagewashed with brine
9. 9
   Séchagedried (Na2SO4)
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated onto silica gel

Mode opératoire

To a round bottom flask was added (R)-3-(2,6-dichloropyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one (364 mg, 1.31 mmol) followed by the addition of DCM (10.8 mL). The reaction mixture was then cooled to 0° C. in a (ice/water bath) under nitrogen. To this cold solution was added tetrafluoroboric acid (0.20 mL, 1.31 mmol, 50% aqueous solution) followed by the addition of trimethylsilyldiazomethane (1.96 mL, 3.93 mmol, 2 M in hexanes) divided into 3 portions added 20 min apart. A second addition of trimethylsilyldiazomethane in hexanes (1.96 mL, 3.93 mmol, 2 M in hexanes) again divided into 3 portions added 20 min apart was added. Reaction mixture was quenched with water and diluted with DCM. Phases paritioned and the aqueous phase extracted with DCM. Organic phases combined and washed with brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (R)-3-(2,6-dichloropyrimidin-4-yl)-4-((R)-1-methoxyethyl)oxazolidin-2-one (119 mg, 0.41 mmol, 31% yield) as a colorless oil which crystallizes upon standing. 1H NMR (400 MHz, CDCl3) δ 1.09 (d, J=6.50 Hz, 3H) 3.44 (s, 3H) 4.09 (qd, J=6.46, 4.16 Hz, 1H) 4.38-4.49 (m, 1H) 4.60 (dd, J=9.49, 2.84 Hz, 1H) 4.99 (ddd, J=8.50, 3.95, 2.96 Hz, 1H) 8.23 (s, 1H). LCMS m/z 292.0 (M+H)+, Rt 0.86 min.

Source