반응 #85760

반응 방정식

2,4,5-Trifluoropyrimidine

EtOAc Heptane

(R)-4-((R)-1-(tert-butoxy)ethyl)oxazolidin-2-one

sodium hydride

→

(R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2,5-difluoropyrimidin-4-yl)oxazolidin-2-one

수율 68.1%

용매

DMF

반응 조건

후처리

1. 1
   workup.ADDITIONwas added
2. 2
   온도to warm to RT
3. 3
   workup.STIRRINGstirred for 1 hr at RT
4. 4
   기타The reaction mixture was quenched with the slow addition of saturated solution of NH4Cl
5. 5
   추출the aqueous mixture extracted with EtOAc
6. 6
   세척washed with water, brine
7. 7
   건조dried (Na2SO4)
8. 8
   여과filtered
9. 9
   농축concentrated onto silica gel

실험 절차

To a solution of (R)-4-((R)-1-(tert-butoxy)ethyl)oxazolidin-2-one (6.35 g, 33.9 mmol) in DMF (170 mL) under a nitrogen atmosphere at 0° C. was added sodium hydride (2.14 g, 50.9 mmol, 60%) portion wise over 3 minutes. The reaction mixture was then stirred for 2 hr at 0° C. whereupon 2,4,5-Trifluoropyrimidine (5 g, 37.3 mmol) was added and the reaction mixture allowed to stir 75 minutes at 0° C. then the mixture was allowed to warm to RT and stirred for 1 hr at RT. The reaction mixture was quenched with the slow addition of saturated solution of NH4Cl and the aqueous mixture extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 50%) provided a colorless oil of (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2,5-difluoropyrimidin-4-yl)oxazolidin-2-one (6.97 g, 23.1 mmol, 68% yield) which crystallizes upon standing. 1H NMR (400 MHz, CDCl3) 1.10 (d, J=6.26 Hz, 3H) 1.18 (s, 9H) 4.25-4.35 (m, 1H) 4.49-4.62 (m, 2H) 4.65-4.73 (m, 1H) 8.45 (d, J=1.57 Hz, 1H). LCMS m/z 246.1 (-t-butyl fragment) (M+H)+, Rt 0.91 min.

출처