Reaktion #798619

Reaktionsgleichung

n-butyllithium

hexane

diisopropylamine

2,6-dichloro-3-iodopyridine

HCl

dry ice

K2CO3

CH3I

→

title compound

Ausbeute 11.0%

Methyl 2,6-dichloro-4-iodonicotinate

Ausbeute 11.0%

Lösungsmittel

THF

THF

Et2O

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe resulting mixture was stirred at −78° C. for 2 h
2. 2
   workup.STIRRINGstirred overnight
3. 3
   SonstigeThe resulting mixture was quenched with H2O
4. 4
   Waschenthe organic phase was washed with H2O
5. 5
   Extraktionextracted with CHCl3 (3×)
6. 6
   Waschenwashed with brine
7. 7
   Trocknendried over MgSO4
8. 8
   Sonstigeevaporated
9. 9
   workup.ADDITIONwere added
10. 10
    workup.STIRRINGThe reaction mixture was stirred at RT for 3 h
11. 11
    ExtraktionThe aqueous phase was extracted with Et2O
12. 12
    Waschenthe combined organic layers were washed with H2O and brine
13. 13
    Trocknendried over MgSO4
14. 14
    Sonstigeevaporated
15. 15
    SonstigeThe residue was purified by chromatography on SiO2

Vorschrift

A solution of n-butyllithium in hexane (1.6M, 120 mL, 192 mmol) was added dropwise to a solution of diisopropylamine (31.2 mL, 219 mmol) in THF (200 mL) at −78° C. and the mixture was stirred for 30 min. A solution of 2,6-dichloro-3-iodopyridine (50.0 g, 183 mmol) in THF (100 mL) was added dropwise to the reaction mixture at −78° C. and the resulting mixture was stirred at −78° C. for 2 h. After adding dry ice to the reaction mixture, the mixture was warmed to RT and stirred overnight. The resulting mixture was quenched with H2O and the organic phase was washed with H2O. The combined aqueous phase was acidified with HCl and extracted with CHCl3 (3×). The organic phases were combined, washed with brine, dried over MgSO4, and evaporated. After the residue was dissolved into DMF (500 mL), K2CO3 (39.2 g, 284 mmol) and CH3I (17.73 mL, 284 mmol) were added. The reaction mixture was stirred at RT for 3 h. To the resulting mixture was added 1N HCl and Et2O. The aqueous phase was extracted with Et2O and the combined organic layers were washed with H2O and brine, dried over MgSO4 and evaporated. The residue was purified by chromatography on SiO2 to give the title compound as a white solid (7.24 g, 11%). 1H NMR (500 MHz, CDCl3) δ ppm 3.99 (s, 3H), 7.77 (s, 1H). [M+H] calc'd for C7H4Cl1NO2, 332. found, 332.

Quelle