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

HRID 561022노트

반응식

HRID 561022 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

HCID 667383455-Cyclopropyl-2-fluoro-3-iodopyridine수율 68%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-5670428a1cc94c55bd90959a66a6f344
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063212B2

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