반응 #2267152

반응 방정식

product

[(3R)-3-(5-Chloro-2-cyano-4-fluorophenoxy)-3-(3-furanyl)propyl]-carbamic acid 1,1-dimethylethyl ester

sodium bicarbonate

fumaric acid

→

title compound

수율 40.0%

2-[[(1R)-3-Amino-1-(3-furanyl)propyl]oxy]-4-chloro-5-fluorobenzonitrile fumarate

수율 40.0%

용매

HCl

dioxan

반응 조건

후처리

1. 1
   기타The reaction was placed in an ice-bath
2. 2
   추출The mixture wa extracted with ethyl acetate (3×50 ml)
3. 3
   세척the combined extracts were washed with water (20 ml)
4. 4
   건조dried (sodium sulphate)
5. 5
   기타evaporated in vacuo
6. 6
   기타The residue was chromatographed on flash silica
7. 7
   세척eluting with 5% 7N ammonia in methanol in dichloromethane
8. 8
   workup.DISSOLUTIONThe product was dissolved in methanol (5 ml)
9. 9
   workup.STIRRINGStirred for 10 minutes
10. 10
    기타then removed the solvent in vacuo
11. 11
    기타triturated the solid residue with a little ethyl acetate
12. 12
    여과The white solid was filtered off
13. 13
    기타dried

실험 절차

The product from step (c) (150 mg, 0.3 mmol) was dissolved in 4M HCl in dioxan (10 ml) and stirred at room temperature for 10 minutes. The reaction was placed in an ice-bath and aqueous saturated sodium bicarbonate solution (30 ml) added cautiously. The mixture wa extracted with ethyl acetate (3×50 ml) and the combined extracts were washed with water (20 ml), dried (sodium sulphate) and evaporated in vacuo. The residue was chromatographed on flash silica, eluting with 5% 7N ammonia in methanol in dichloromethane. The product was dissolved in methanol (5 ml) and treated with one equivalent of fumaric acid. Stirred for 10 minutes then removed the solvent in vacuo and triturated the solid residue with a little ethyl acetate. The white solid was filtered off and dried to give the title compound (50 mg, 40%).

출처