반응 #85622

반응 방정식

(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

수율 31.0%

용매

EtOAc Heptane

반응 조건

후처리

1. 1
   workup.ADDITIONadded 20 min apart
2. 2
   workup.ADDITIONadded 20 min
3. 3
   workup.ADDITIONapart was added
4. 4
   기타Reaction mixture
5. 5
   기타was quenched with water
6. 6
   workup.ADDITIONdiluted with DCM
7. 7
   추출the aqueous phase extracted with DCM
8. 8
   세척washed with brine
9. 9
   건조dried (Na2SO4)
10. 10
    여과filtered
11. 11
    농축concentrated onto silica gel

실험 절차

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.

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