Propargyl alcohol → 3-(6-Aminopyridin-3-yl)prop-2-yn-1-ol

HRID 1355500ノート

反応式

HRID 1355500 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.N1CCCC1.[CH2:14]([OH:17])[C:15]#[CH:16]>>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:16]#[C:15][CH2:14][OH:17])=[CH:6][CH:7]=1

参加物

4

反応物 3

HCID 7859Propargyl alcoholHCID 31268PyrrolidineHCID 706222-Amino-5-bromopyridine

生成物 1

HCID 185068563-(6-Aminopyridin-3-yl)prop-2-yn-1-ol

反応条件

温度
80 °C

実験手順

2-Amino5-bromopyridine (7-1), 10.0 g (57.8 mmol) was stirred in pyrrolidine (96.5 mL, 1.16 mol, 20 equiv) in a flame dried round bottom flask under argon. Propargyl alcohol (10.1 mL, 173 mmol) and tetrakis triphenylphosphine palladium(0) (1.34 g, 1.16 mmol) were added and the solution was degassed 3× by alternating vacuum/Ar. Heat to 80° C. After 18 h the bulk of the pyrrolidine was removed in vacuo and the residue was diluted with water. Extract with CH2Cl2 three times, and the extracts were dried over Na2SO4, filtered and concentrated to provide impure product. The aqueous layer was further extracted ten times with CH2Cl2/nBuOH (95:5). The extracts were dried over Na2SO4, filtered and concentrated. The two samples were combined and were purified in two batches by flash column chromatography (gradient: CH2Cl2 to CH2Cl2/MeOH, 90:10). The product was triurated with ice cold CH2Cl2, filtered, and washed with ice cold CH2Cl2. Afforded the titled compound as a pale yellow solid. 1H NMR (CD3OD) δ 7.96 (d, 1H, J=2.2 Hz), 7.45 (dd, 1H, J=2.4, 8.8 Hz), 6.51 (d, 1H, J=8.8 Hz), 4.36 (s, 2H).

後処理

  1. customdried round bottom flask under argon
  2. customthe solution was degassed 3×
  3. customAfter 18 h the bulk of the pyrrolidine was removed in vacuo
  4. additionthe residue was diluted with water
  5. extractionExtract with CH2Cl2 three times
  6. dry with materialthe extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide impure product
  10. extractionThe aqueous layer was further extracted ten times with CH2Cl2/nBuOH (95:5)
  11. dry with materialThe extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customwere purified in two batches by flash column chromatography (gradient: CH2Cl2 to CH2Cl2/MeOH, 90:10)
  15. filtrationfiltered
  16. washwashed with ice cold CH2Cl2

出典と根拠

ORDレコード
ord-fdd8e96b47b048f184986589454680c0
出典データセット
uspto-grants-2003_07
特許番号
US06586424B2

反応ノート

読み込み中…