Reaktion #218055

Reaktionsgleichung

4-[1,3]dioxolan-2-yl-2-phenol

4-[1,3]dioxolan-2-yl-2-methoxyphenol

5-chloropyrazine-2-carbonitrile

K2CO3

→

title compound

Ausbeute 81.8%

5-(4-Formylphenoxy)pyrazine-2-carbonitrile

Ausbeute 81.8%

Lösungsmittel

DMA

isooctane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturCool to room temperature
2. 2
   Sonstigequench with water (100 mL)
3. 3
   ExtraktionExtract with dichloromethane (3×100 mL)
4. 4
   WaschenWash the
5. 5
   Extraktionextract with saturated aqueous NaHCO3 (1×50 mL) and brine (1×75 mL)
6. 6
   TrocknenDry the organic layer over Na2SO4
7. 7
   Filtrationfilter
8. 8
   Einengenconcentrate
9. 9
   SonstigePurify by flash chromatography
10. 10
    Wascheneluting with 0-30% ethyl acetate in hexanes
11. 11
    EinengenConcentrate the eluant
12. 12
    workup.ADDITIONDilute the reaction mixture with water (50 mL)
13. 13
    ExtraktionExtract with dichloromethane (2×100 mL)
14. 14
    WaschenWash the
15. 15
    Extraktionextract with saturated aqueous NaHCO3 (1×50 mL)
16. 16
    Trocknendry over Na2SO4
17. 17
    Filtrationfilter
18. 18
    Einengenconcentrate
19. 19
    SonstigePurify by flash chromatography
20. 20
    Wascheneluting with 30% ethyl acetate in hexanes

Vorschrift

Dissolve 4-[1,3]dioxolan-2-yl-2-phenol (Example 388, Part C2) (1.70 g, 10.2 mmol), 5-chloropyrazine-2-carbonitrile (Example 404, Part A) (1.50 g, 10.7 mmol) and K2CO3 (3.71 g, 26.9 mmol) in DMA (27.0 mL) and isooctane (13.4 mL). Heat at 110° C. for about 2.25 hours. Cool to room temperature and quench with water (100 mL). Extract with dichloromethane (3×100 mL). Wash the extract with saturated aqueous NaHCO3 (1×50 mL) and brine (1×75 mL). Dry the organic layer over Na2SO4, filter and concentrate. Purify by flash chromatography, eluting with 0-30% ethyl acetate in hexanes. Concentrate the eluant, then take the solid up in 88% formic acid (46 mL) and stir at room temperature for 4 hours. Dilute the reaction mixture with water (50 mL). Extract with dichloromethane (2×100 mL). Wash the extract with saturated aqueous NaHCO3 (1×50 mL), dry over Na2SO4, filter and concentrate. Purify by flash chromatography eluting with 30% ethyl acetate in hexanes to give the title compound (1.88 g, 77.7%): TOF MS ES+ 225.1 (M)+, HRMS calcd for C12H7N3O2 225.0538 (M)+, found 225.0527, time 0.38 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 20-99% over 23 min], tR=11.5 min, 100% purity.

Quelle