Tetrahydrofuran → (αR)-3-Chloro-α-methyl-6-isoquinolinemethanol

HRID 1895779ノート

反応式

HRID 1895779 の反応式
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C:12](=[O:14])[CH3:13])=[CH:7][CH:6]=2.C([O-])=O.[Na+].O1CCCC1>O.CC1C=CC(C(C)C)=CC=1.CC1C=CC(C(C)C)=CC=1.Cl[Ru]Cl.Cl[Ru]Cl.CC1C=CC(S(N[C@@H]([C@H](N)C2C=CC=CC=2)C2C=CC=CC=2)(=O)=O)=CC=1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C@H:12]([OH:14])[CH3:13])=[CH:7][CH:6]=2

参加物

7

反応物 3

HCID 8028TetrahydrofuranHCID 2723810Sodium FormateHCID 866758631-(3-Chloroisoquinolin-6-yl)ethanone

生成物 1

HCID 86675864(αR)-3-Chloro-α-methyl-6-isoquinolinemethanol収率 92.9%

試薬・触媒・溶媒 3

HCID 2734565N-((1R,2R)-2-Amino-1,2-diphenylethyl)-4-methylbenzene-1-sulfonamide触媒HCID 10908223Dichloro(p-cymene)ruthenium(II) dimer触媒HCID 962Water溶媒

反応条件

温度
70 °C

実験手順

Dichloro(p-cymene)ruthenium(II) dimer (3 mg, 0.005 mmol) and (1R,2R)-(−)-N-p-tosyl-1,2-diphenylethylenediamine (4.4 mg, 0.012 mmol) was suspended in degassed water (2 mL) and the mixture was degassed with nitrogen for 15 minutes. The mixture was stirred at 70° C. under nitrogen for 90 minutes. The resulting yellow solution was cooled to room temperature. 1-(3-Chloro-isoquinolin-6-yl)-ethanone (206 mg, 1 mmol), sodium formate (340 mg, 5 mmol) and degassed tetrahydrofuran (1 mL) were added and the reaction mixture was degassed with nitrogen for 5 minutes. The reaction mixture was vigorously stirred at 40° C. for 2.5 hours. The reaction mixture was cooled to room temperature and was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 4:1 to 2:1 to afford the title compound (193 mg, 92%) as a white solid. 1H NMR (300 MHz, CDCl3) δ1.60 (d, J=5.9 Hz, 3H), 2.14 (d, J=3.1 Hz, 1H), 5.08-5.16 (m, 1H), 7.63 (dd, J=8.6, 1.6 Hz, 1H), 7.72 (s, 1H), 7.77 (br s, 1H), 7.96 (d, J=8.6 Hz, 1H), 9.04 (s, 1H). LCMS (m/z) 208/210 [M+H], Tr=4.25 min.

後処理

  1. customthe mixture was degassed with nitrogen for 15 minutes
  2. temperatureThe resulting yellow solution was cooled to room temperature
  3. additionwere added
  4. customthe reaction mixture was degassed with nitrogen for 5 minutes
  5. stirringThe reaction mixture was vigorously stirred at 40° C. for 2.5 hours
  6. temperatureThe reaction mixture was cooled to room temperature
  7. extractionwas extracted with ethyl acetate
  8. customThe organic layer was separated
  9. washwashed with water and brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-16360fde20984c8baa0a0f4512d31eb0
出典データセット
uspto-grants-2013_08
特許番号
US08513184B2

反応ノート

読み込み中…