Hydrochloric Acid → 5-Methyl-6-((2,2,2-trifluoroethyl)amino)nicotinic acid

HRID 715412Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 715412
F[C:2]1[C:11]([CH3:12])=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][N:3]=1.[F:13][C:14]([F:18])([F:17])[CH2:15][NH2:16].Cl>CN1CCCC1=O.CO.[OH-].[Na+]>[CH3:12][C:11]1[C:2]([NH:16][CH2:15][C:14]([F:18])([F:17])[F:13])=[N:3][CH:4]=[C:5]([CH:10]=1)[C:6]([OH:8])=[O:7]

Komponenten

7

Edukt 3

HCID 313Hydrochloric AcidHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 53419770Methyl 6-fluoro-5-methylpyridine-3-carboxylate

Produkt 1

HCID 898739845-Methyl-6-((2,2,2-trifluoroethyl)amino)nicotinic acidAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
220 °C

Versuchsvorschrift

A mixture of methyl 6-fluoro-5-methylnicotinate (2.00 g, 11.8 mmol, Step-1 of Amine-36) and 2,2,2-trifluoroethanamine (9.37 g, 95 mmol) in N-methylpyrrolidone (24 mL) is stirred at 220° C. for 2.5 hours under microwave irradiation. The mixture is diluted with MeOH (30 mL), and 2 M aqueous sodium hydroxide solution (15 mL) is added to the mixture. After stirring at 50° C. for 1 hour, the mixture is acidified by 2 M hydrochloric acid, and extracted with EtOAc/hexane (100 mL×3). The combined organic layer is washed with water (100 mL), and dried over sodium sulfate. After filtration, the filtrate is concentrated in vacuo. The residue is crystallized from diisopropyl ether to give 884 mg (32%) of the title compound as a pale pink solid.

Aufarbeitung

  1. additionis added to the mixture
  2. stirringAfter stirring at 50° C. for 1 hour
  3. extractionextracted with EtOAc/hexane (100 mL×3)
  4. washThe combined organic layer is washed with water (100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtration
  7. concentrationthe filtrate is concentrated in vacuo
  8. customThe residue is crystallized from diisopropyl ether

Quellen und Nachweise

ORD-Eintrag
ord-09c35eb43bf841bbbfdf52a0ad8b0676
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09187475B2

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