Triethylamine → Methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinate

HRID 72429

Reaktionsgleichung

Reaktionsgleichung von HRID 72429
Cl.[OH:2][CH:3]1[CH2:6][NH:5][CH2:4]1.C(N(CC)CC)C.Cl[C:15]1[N:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:16]=1[C:17]([O:19][CH3:20])=[O:18]>O1CCCC1.CO>[Cl:25][C:22]1[CH:23]=[N:24][C:15]([N:5]2[CH2:6][CH:3]([OH:2])[CH2:4]2)=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18]

Komponenten

5

Edukt 3

HCID 8471Triethylamine2×HCID 27592903-Hydroxyazetidine hydrochloride2×HCID 2764318Methyl 2,5-Dichloronicotinate

Produkt 1

HCID 67958303Methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinateAusbeute 76,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21899815MeOH tetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

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).

Aufarbeitung

  1. additionwas added
  2. customat 62° C.
  3. customovernight
  4. temperaturethe reaction mixture was further heated at 80° C. for 28 h
  5. customSolvents were evaporated in vacuo
  6. filtrationThe formed solid was filtered
  7. washwashed with water (500 ml)
  8. customdried in vacuum

Quellen und Nachweise

ORD-Eintrag
ord-25e4a4f6a52f415abe7623234769fe0c
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828987B2

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