반응 #168763

반응 방정식

[1-(5-Bromo-2-fluoro-phenyl)-2,2-difluoro-1-hydroxymethyl-ethyl]-carbamic acid tert-butyl ester

Na2CO3

Racemic 2-chloro-propionyl chloride

→

N-[1-(5-Bromo-2-fluoro-phenyl)-2,2-difluoro-1-hydroxymethyl-ethyl]-2-chloro-propionamide

용매

dichloromethane

HCl

dioxane

반응 조건

후처리

1. 1
   기타The reaction mixture was evaporated
2. 2
   기타to give a white solid which
3. 3
   온도the emulsion was cooled to 0-5° C
4. 4
   온도the reaction mixture was slowly warmed to room temperature
5. 5
   workup.WAITAfter 30 minutes
6. 6
   기타the layers were separated
7. 7
   세척washed with dichloromethane
8. 8
   건조dried over Na2SO4
9. 9
   기타evaporated
10. 10
    기타The crude product was purified on a silica gel column
11. 11
    세척by eluting with heptanes/EtOAc 3/1->2/1
12. 12
    기타to give 632 mg of the
13. 13
    세척first eluting

실험 절차

[1-(5-Bromo-2-fluoro-phenyl)-2,2-difluoro-1-hydroxymethyl-ethyl]-carbamic acid tert-butyl ester [Example 42 step c)](2.21 g, 5.75 mmol) was dissolved in 20 mL HCl solution 4 mol/L in dioxane and stirred at room temperature for 60 minutes. The reaction mixture was evaporated to give a white solid which was directly taken up in 15 mL dichloromethane. 20 mL aqueous Na2CO3 solution (10% w/w) was added and the emulsion was cooled to 0-5° C. Racemic 2-chloro-propionyl chloride (787 mg, 6.20 mmol) was added dropwise and the reaction mixture was slowly warmed to room temperature. After 30 minutes, the layers were separated and washed with dichloromethane. The organic layers were combined, dried over Na2SO4 and evaporated. The crude product was purified on a silica gel column by eluting with heptanes/EtOAc 3/1->2/1 to give 632 mg of the first eluting and 619 mg of the second eluting diastereomer.

출처