반응 #694098

반응 방정식

5-(4-fluoro-3-formylphenylethynyl)nicotinonitrile

N-methyl-β-alaninenitrile

sodium triacetoxyborohydride

→

title compound

수율 43.0%

5-(3-{[(2-Cyanoethyl)methylamino]methyl}-4-fluorophenylethynyl)-nicotinonitrile

수율 43.0%

용매

dichloroethane

반응 조건

후처리

1. 1
   workup.DISSOLUTIONDissolve
2. 2
   기타quench with water (2 mL)
3. 3
   workup.ADDITIONdilute with dichloromethane
4. 4
   추출extract three times with 0.5 N hydrochloric acid, but thin layer chromatography
5. 5
   workup.ADDITIONAdd 1 N sodium hydroxide to the aqueous layer until it
6. 6
   추출is basic then extract twice with ethyl acetate
7. 7
   세척wash with an aqueous saturated solution of sodium chloride
8. 8
   건조dry (sodium sulfate)
9. 9
   여과filter
10. 10
    농축concentrate
11. 11
    기타Purify by silica gel chromatography
12. 12
    세척eluting with 90:10 to 80:20 dichloromethane

실험 절차

Dissolve 5-(4-fluoro-3-formylphenylethynyl)nicotinonitrile, (prepared as described in PREPARATION 38) (100 mg, 0.40 mmol) in dichloroethane (2 mL) and treat with N-methyl-β-alaninenitrile (0.041 mL, 0.44 mmol) and sodium triacetoxyborohydride (110 mg, 0.52 mmol). After stirring for 5.5 h, quench with water (2 mL), dilute with dichloromethane and extract three times with 0.5 N hydrochloric acid, but thin layer chromatography shows some product still remaining in the organic phase. Add 1 N sodium hydroxide to the aqueous layer until it is basic then extract twice with ethyl acetate. Combine the dichloromethane layer with the ethyl acetate extracts and wash with an aqueous saturated solution of sodium chloride, dry (sodium sulfate), filter, and concentrate. Purify by silica gel chromatography, eluting with 90:10 to 80:20 dichloromethane:ethyl acetate, to give the title compound as a white crystalline solid (55 mg, 43%).

출처