Reaktion #332593

Reaktionsgleichung

(2R,6S)-4-[6-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-2,3-difluorophenyl]-2,6-dimethylmorpholine

Intermediate 3

(2R,6S)-4-[6-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-2,3-difluorophenyl]-2,6-dimethylmorpholine

diethyl oxalate

Sec-butyl lithium

→

title compound

Ausbeute 81.0%

Ethyl 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetate

Ausbeute 81.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas cannulated into a −78° C.
2. 2
   Temperaturcooled flask
3. 3
   workup.STIRRINGto stir at −78° C. for 30 minutes
4. 4
   Sonstigequenched cold with 1 ml
5. 5
   Temperaturto warm to room temp
6. 6
   workup.ADDITIONThe reaction was diluted with water
7. 7
   Extraktionextracted twice with ethyl acetate
8. 8
   Waschenwashed twice with brine
9. 9
   Trocknendried over MgSO4
10. 10
    Einengenconcentrated
11. 11
    SonstigeThe residue was purified by silica gel column chromatography

Vorschrift

(2R,6S)-4-[6-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-2,3-difluorophenyl]-2,6-dimethylmorpholine (Intermediate 3, 0.5 g, 1.01 mmol) was dissolved in 10 ml of THF and cooled to −78° C. Sec-butyl lithium (1.358 ml, 1.77 mmol) was added drop wise over 5 minutes. The reaction stirred at −78° C. for 1.5 hours. The reaction mixture was cannulated into a −78° C. cooled flask containing diethyl oxalate (1.370 ml, 10.09 mmol) in 10 ml of THF. The reaction was allowed to stir at −78° C. for 30 minutes; quenched cold with 1 ml sat NH4Cl and allowed to warm to room temp. The reaction was diluted with water and extracted twice with ethyl acetate. The organic layers were combined and washed twice with brine, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography using a gradient of hexanes to ethyl acetate to give the title compound (486 mg, 81% yield) contaminated with diethyl oxalate. This material was taken to the next step without further purification.

Quelle