Potassium Carbonate → 6-bromo-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}quinoline

HRID 273214ノート

反応式

HRID 273214 の反応式
C([C@@H]([C@H](C(O)=O)O)O)(O)=O.[CH3:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:34][CH2:35][C:36]2[CH:45]=[CH:44][C:43]3[C:38](=[CH:39][CH:40]=[C:41]([Br:46])[CH:42]=3)[N:37]=2)(=O)=O)=CC=1>C(#N)C>[Br:46][C:41]1[CH:42]=[C:43]2[C:38](=[CH:39][CH:40]=1)[N:37]=[C:36]([CH2:35][CH2:34][N:13]1[CH2:14][CH2:15][CH2:16][C@H:12]1[CH3:11])[CH:45]=[CH:44]2

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 11858493(R)-2-methylpyrrolidine L-tartrateHCID 865922242-(6-Bromo-2-quinolinyl)ethyl 4-methylbenzenesulfonate

生成物 1

HCID 671046156-bromo-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}quinoline収率 92.2%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

(2R)-2-Methylpyrrolidine L-tartrate (7.00 g, 0.0298 mole, milled), potassium carbonate (9.04 g, 0.0655 mole, milled), and acetonitrile (190 mL) were combined and heated at 60° C. with agitation for 48 hours. The mixture was allowed to cool to 30° C., and treated with the product from Example 42C (8.00 g, 0.0197 mole). The reaction mixture was heated at ˜60° C. for 36 hours and then distilled down to ˜¼ volume, and isopropyl acetate (200 mL) was added. The mixture was washed with 5% NaHCO3 aq. solution (200 mL×2), and 25% brine (200 mL). The upper organic was dried over anhydrous sodium sulphate, filtered, and the filtrate was concentrated to dryness. The crude product was purified with a short-path silica gel column eluted with heptane:ethyl acetate:TEA (60:40:1) to give 5.8 g (92% yield) of product as an oil, which solidified on standing; mp 49-50° C. (uncorrected); MS (ESI): 319, 311 (M+H)+; 1H-NMR (CDCl3) δ 7.95 (1H, d, J=8.5 Hz), 7.91 (1H, d, J=2.2 Hz), 7.89 (1H, d, J=8.9 Hz), 7.72 (1H, dd, J=8.9, 2.2 Hz), 7.35 (1H, d, J=8.5 Hz), 3.23 (2H, m), 3.18 (2H, m), 2.55 (1H, m), 2.38 (1H, m), 2.25 (1H, q, J=8.9 Hz), 1.93 (1H, m), 1.80 (1H, m), 1.71 (1H, m), 1.42 (1H, m), 1.11 (3H, d, J=6.0 Hz); 13C-NMR (CDCl3) δ 161.3, 146.1, 134.7, 132.3, 130.3, 129.2, 127.6, 122.2, 119.2, 59.9, 54.0, 53.6, 38.6, 33.0, 22.0, 19.4.

後処理

  1. temperatureto cool to 30° C.
  2. temperatureThe reaction mixture was heated at ˜60° C. for 36 hours
  3. distillationdistilled down
  4. additionwas added
  5. washThe mixture was washed with 5% NaHCO3 aq. solution (200 mL×2), and 25% brine (200 mL)
  6. dry with materialThe upper organic was dried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated to dryness
  9. customThe crude product was purified with a short-path silica gel column
  10. washeluted with heptane:ethyl acetate:TEA (60:40:1)

出典と根拠

ORDレコード
ord-a7c5242d5a884cbfa4d7ed77e291303a
出典データセット
uspto-grants-2008_11
特許番号
US07456196B2

反応ノート

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