Iodine → 5-Cyclopropyl-2-fluoro-3-iodopyridine

HRID 561022ノート

反応式

HRID 561022 の反応式
[CH:1]1([C:4]2[CH:5]=[CH:6][C:7]([F:10])=[N:8][CH:9]=2)[CH2:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].[I:19]I.S([O-])([O-])(=O)=S.[Na+].[Na+]>C1COCC1.O>[CH:1]1([C:4]2[CH:5]=[C:6]([I:19])[C:7]([F:10])=[N:8][CH:9]=2)[CH2:3][CH2:2]1

参加物

7

反応物 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 2724682Lithium diisopropylamideHCID 576908315-Cyclopropyl-2-fluoropyridine

生成物 1

HCID 667383455-Cyclopropyl-2-fluoro-3-iodopyridine収率 68%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Cool a solution of 5-cyclopropyl-2-fluoro-pyridine (1.3 g, 9.5 mmol) in THF (20 mL) to −75° C. in a dry ice-acetone bath under nitrogen. Add lithium diisopropylamide (2 M in THF, 6 mL, 12 mmol) over a period of 30 min. Stir the mixture for an additional 3 hours. Add iodine (2.9 g, 11.4 mmol, dissolved in 50 mL of THF) and stir the mixture for 2 hours. Add water (100 mL) and allow the temperature to rise to room temperature over 1 hour while stirring. Treat the mixture with saturated aqueous sodium thiosulfate solution (50 mL). Extract the solution with ether. Concentrate the solution in vacuo to brown oil. Purify by column chromatography (hexane to 20% ethyl acetate in hexane) to afford the title compound (1.7 g, 68%) as a yellow oil. 1H NMR (400 MHz-CDCl3) δ 8.03 (dd, J=3, 8 Hz, 1H), 7.99 (s, 1H), 0.91-1.00 (m, 2H), 0.71-0.78 (m, 2H).

後処理

  1. waitto rise to room temperature over 1 hour
  2. stirringwhile stirring
  3. extractionExtract the solution with ether
  4. concentrationConcentrate the solution in vacuo to brown oil
  5. customPurify by column chromatography (hexane to 20% ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-5670428a1cc94c55bd90959a66a6f344
出典データセット
uspto-grants-2011_11
特許番号
US08063212B2

反応ノート

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