Reaktion #159611

Reaktionsgleichung

3-Hydroxyazetidine hydrochloride

triethylamine

3-Hydroxyazetidine hydrochloride

triethylamine

Methyl 2,5-dichloronicotinate

→

title compound ( D62 )

Ausbeute 76.6%

methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinate

Ausbeute 76.6%

Lösungsmittel

tetrahydrofuran methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Sonstigeat 62° C.
3. 3
   Sonstigeovernight
4. 4
   Temperaturthe reaction mixture was further heated at 80° C. for 28 h
5. 5
   SonstigeSolvents were evaporated in vacuo
6. 6
   FiltrationThe formed solid was filtered
7. 7
   Waschenwashed with water (500 ml)
8. 8
   Sonstigedried in vacuum

Vorschrift

To a mixture of 3-Hydroxyazetidine hydrochloride (37.17 g, 0.339 mol) and triethylamine (70.93 ml, 0.508 mol) in tetrahydrofuran/methanol (840/280 ml) Methyl 2,5-dichloronicotinate (70 g, 0.339 mol) was added and the resulting mixture was heated at 75° C. for 4 hours then at 62° C. overnight. 3-Hydroxyazetidine hydrochloride (3.7 g, 0.03 mol) and triethylamine (23.60 ml, 0.16 mol) were added and the reaction mixture was further heated at 80° C. for 28 h. Solvents were evaporated in vacuo. The residue was taken in dichloromethane (400 ml) and water (500 ml). The formed solid was filtered, washed with water (500 ml) and dried in vacuum to afford a first batch of the title compound (D62) (63 g).

Quelle