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

HRID 528877ノート

反応式

HRID 528877 の反応式
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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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)+.

後処理

  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×)

出典と根拠

ORDレコード
ord-9ea0f0328a6b4a6f83a53babaacab1e0
出典データセット
uspto-grants-2016_05
特許番号
US09346795B2

反応ノート

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