2-Chloro-N,N-dimethylethylamine → (S)-1-(3-((2-(Dimethylamino)ethoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone

HRID 528877노트

반응식

HRID 528877 반응식
Cl[CH2:2][CH2:3][N:4]([CH3:6])[CH3:5].[H-].[Na+].[OH:9][CH2:10][C@@H:11]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][N:12]1[C:21](=[O:23])[CH3:22].[NH4+].[Cl-]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-].CCOC(C)=O>[CH3:5][N:4]([CH3:6])[CH2:3][CH2:2][O:9][CH2:10][C@@H:11]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][N:12]1[C:21](=[O:23])[CH3:22]

참가 물질

8

반응물 4

HCID 79012-Chloro-N,N-dimethylethylamineHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86718900(S)-1-(3-(Hydroxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone

생성물 1

HCID 86718901(S)-1-(3-((2-(Dimethylamino)ethoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone수율 54%

시약·촉매·용매 3

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

To 2-chloro-N,N-dimethylethanamine (63 mg, 0.59 mmol) in DMF (1.0 mL) was added NaH (156 mg, 3.90 mmol, 60% suspension in mineral oil) at 0° C. After stirring for 20 min at 0° C., (S)-1-(3-(hydroxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (40 mg, 0.20 mmol) was added, and the resulting suspension was stirred at room temperature for 10 min. TBAI (7 mg, 0.019 mmol) was then added, and the reaction mixture was heated at 70° C. for 1.5 h. The mixture was then poured into sat. aq. NH4Cl solution and EtOAc. The layers were separated, and the organic layer was washed with sat. aq. NH4Cl solution. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed with sat. aq. NaCl solution and dried over Na2SO4. Filtration and concentration in vacuo provided a crude oil which was triturated with hexanes (3×) to give the title compound (29 mg, 54%) as a pale yellow oil. MS(ESI+) m/z 206.1 (M+H)+.

후처리

  1. stirringthe resulting suspension was stirred at room temperature for 10 min
  2. temperaturethe reaction mixture was heated at 70° C. for 1.5 h
  3. customThe layers were separated
  4. washthe organic layer was washed with sat. aq. NH4Cl solution
  5. extractionThe aqueous layer was extracted with EtOAc (3×)
  6. washthe combined organics were washed with sat. aq. NaCl solution
  7. dry with materialdried over Na2SO4
  8. filtrationFiltration and concentration in vacuo
  9. customprovided a crude oil which
  10. customwas triturated with hexanes (3×)

출처 및 근거

ORD 기록
ord-9ea0f0328a6b4a6f83a53babaacab1e0
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346795B2

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