Hydrochloric Acid → 2-((Dimethylamino)methyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethyl ester

HRID 2093725노트

반응식

HRID 2093725 반응식
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12](=O)[CH3:13].Cl[C:16](=O)[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].Cl.C[CH2:26][N:27]([CH:31](C)C)[CH:28](C)C.[Cl-].C[NH2+]C>CCOC(C)=O.O.CC#N>[CH2:21]([O:20][C:18]([C:17]1[C:16]([CH2:26][N:27]([CH3:31])[CH3:28])=[N:1][C:2]2[C:3]([C:12]=1[CH3:13])=[CH:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=2)=[O:19])[CH3:22]

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 118931Ethyl 3-chloro-3-oxopropionateHCID 12954980Dimethylazanium;chlorideHCID 468355001-(2-Amino-4-(trifluoromethyl)phenyl)ethan-1-one

생성물 1

HCID 665840092-((Dimethylamino)methyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethyl ester수율 46%

시약·촉매·용매 3

HCID 962Water용매2회HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

A mixture of 1.0 g (5.0 mmol) 1-(2-amino-4-(trifluoromethyl)phenyl)ethanone, 3.4 ml (25.0 mmol) ethyl 3-chloro-3-oxopropanoate and 435 μl (5.0 mmol) conc. hydrochloric acid was heated in a sealed vessel in the MW to 100° C. for 30 min. The mixture was subsequently diluted with EtOAc and water. The organic phase was separated, washed with a 1M aq. NaHCO3 sol., dried over MgSO4 and concentrated in a vacuum. The raw product (1.14 g) obtained after CC (EtOAc/hexane 3:17) of the residue was dissolved in MeCN (6 ml) and 2.7 ml (15.5 mmol) DIPEA and 838 mg (10.3 mmol) dimethylammoniumchlorid were added. The mixture was subsequently stirred at RT for 16 h. After cooling to RT, the mixture was diluted with water and extracted with EtOAc. The organic layer was extracted twice a 2N aq. HCl and water. The combined aqueous layers were basified with Na2CO3 and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum. As residue 776 mg (2.3 mmol, 46%) 2-((dimethylamino)methyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethyl ester was obtained.

후처리

  1. customThe organic phase was separated
  2. washwashed with a 1M aq. NaHCO3 sol.
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in a vacuum
  5. customThe raw product (1.14 g) obtained after CC (EtOAc/hexane 3:17) of the residue
  6. temperatureAfter cooling to RT
  7. extractionextracted with EtOAc
  8. extractionThe organic layer was extracted twice a 2N aq. HCl and water
  9. extractionextracted with EtOAc
  10. washThe organic layer was washed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuum

출처 및 근거

ORD 기록
ord-cb751411734e4e15bc8e6149687e5272
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445512B2

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