Hydrochloric Acid → 4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile

HRID 1518492노트

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HRID 1518492 반응식
[F:1][C:2]1[CH:9]=[C:8](I)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[Cl:11][C:12]1[C:13]([OH:19])=[CH:14][C:15](=[O:18])[NH:16][CH:17]=1.COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.O.[Cu]I>[Cl:11][C:12]1[C:13]([OH:19])=[CH:14][C:15](=[O:18])[N:16]([C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=2)[CH:17]=1

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27745182-Fluoro-4-iodobenzonitrileHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 54679224Gimeracil

생성물 1

HCID 673665324-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile수율 74.7%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

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온도
140 °C

실험 절차

A mixture of 2-fluoro-4-iodobenzonitrile (4000 mg, 16.19 mmol), 5-chloro-4-hydroxypyridin-2(1H)-one (2357 mg, 16.19 mmol), 4,7-dimethoxy-1,10-phenanthroline (778 mg, 3.24 mmol), copper(I) iodide (617 mg, 3.24 mmol) and potassium carbonate (4476 mg, 32 4 mmol) in DMSO (40 mL) was stirred at 140° C. under N2 for 3 h. After cooled to rt, the reaction mixture was diluted with H2O (50 mL) and added 1N HCl to adjust the pH to ˜2 (pH paper). The resulting mixture was extracted with EtOAc (400 mL, 2×). The combined extracts were dried (Na2SO4) and evaporated under reduced pressure to give black oil. The residue was purified by flash chromatography (SiO2, 0 to 7% MeOH/CH2Cl2) to give brown oil (3.2 g, 43.3%). MS (ESI) 265 (M+H).

후처리

  1. temperatureAfter cooled to rt
  2. extractionThe resulting mixture was extracted with EtOAc (400 mL, 2×)
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. customevaporated under reduced pressure
  5. customto give black oil
  6. customThe residue was purified by flash chromatography (SiO2, 0 to 7% MeOH/CH2Cl2)

출처 및 근거

ORD 기록
ord-da7e54358e6340fdbb492fc3fbd4f529
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232404B2

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