Morpholine → 4-(5-Bromopyridin-3-yl)morpholine

HRID 44986

反応式

HRID 44986 の反応式
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.O1CCOCC1.[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.CC(C)([O-])C.[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:8][C:6]1[CH:7]=[C:2]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:3]=[N:4][CH:5]=1

参加物

6

反応物 4

HCID 8083MorpholineHCID 312751,4-DioxaneHCID 693693,5-DibromopyridineHCID 23676156Sodium t-butoxide

生成物 1

HCID 467396144-(5-Bromopyridin-3-yl)morpholine収率 41.1%

試薬・触媒・溶媒 1

HCID 178418397HCID 178418397、化合物触媒

反応条件

温度
80 °C

実験手順

To a solution of [3,5-dibromopyridine (1000 mg, 0.004 mol) in 1,4-dioxane (8 mL, 0.1 mol), morpholine (400 mg, 0.004 mol) and sodium tert-butoxide (400 mg, 0.004 mol) were added. The reaction was bubbled with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (200 mg, 0.0002 mol) was added and nitrogen was bubbled through for couple of minutes. The mixture was heated at 80° C. overnight. The reaction was allowed to cool to rt and was then partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated to give a crude residue. The crude product was purified by FCC on silica gel eluting with 1:1, EtOAC:Hexane gave to give 4-(5-bromopyridin-3-yl)morpholine as a viscous oil (400 mg, 40%). 1H NMR (400 MHz, CDCl3): 8.2 (s, 1H), 8.1 (s, 1H), 7.2 (s, 1H), 3.8 (m, 4H), 3.2 (m, 4H).

後処理

  1. customThe reaction was bubbled with nitrogen
  2. customnitrogen was bubbled through for couple of minutes
  3. temperatureto cool to rt
  4. customwas then partitioned between water and ethyl acetate
  5. washThe organic layer was washed with saturated sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude residue
  10. customThe crude product was purified by FCC on silica gel eluting with 1:1, EtOAC
  11. customHexane gave

出典と根拠

ORDレコード
ord-f68c61ed84274e17b1717f97a24de537
出典データセット
uspto-grants-2013_09
特許番号
US08541425B2

関連ノート

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