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

HRID 715412노트

반응식

HRID 715412 반응식
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]

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 887Methanol용매HCID 13387N-methyl-2-pyrrolidone용매HCID 14798Sodium Hydroxide용매

반응 조건

온도
220 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-09c35eb43bf841bbbfdf52a0ad8b0676
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187475B2

반응 노트

불러오는 중…