Dimethylformamide → 6-Fluoroquinoline-4-carbonitrile

HRID 1094639

반응식

HRID 1094639 반응식
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH3:13][N:14](C=O)C>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[F:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][CH:3]=[C:2]2[C:13]#[N:14]

참가 물질

6

반응물 2

HCID 6228DimethylformamideHCID 27365864-Chloro-6-fluoroquinoline

생성물 1

HCID 451233306-Fluoroquinoline-4-carbonitrile

시약·촉매·용매 3

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 4-chloro-6-fluoroquinoline (APOLLO) (1120 mg, 6.17 mmol), zinc cyanide (1450 mg, 12.3 mmol) and palladium (0) tetrakis(triphenylphosphine)(713 mg, 0.617 mmol) in dry DMF (15 ml) was treated with microwave (160° C., 30 min.). The mixture was diluted with ethyl acetate and filtered through a pad of celite. To the filtrate was added toluene (ca.20 ml) and the organic layer was washed with water (×2), brine, dried and concentrated in vacuo to give crude product. The crude product was purified by column chromatography on silica gel (ca. 250 g) with hexane-ethyl acetate (3:1) to give the title compound (880 mg, white solid). 1H NMR (270 MHz, CDCl3) δ ppm 7.60-7.70 (1H, m), 7.75-7.79 (1H, m), 7.81-7.87 (1H, m), 8.20-8.28 (1H, m), 9.00-9.05 (1H, m).

후처리

  1. additionwas treated with microwave (160° C., 30 min.)
  2. filtrationfiltered through a pad of celite
  3. additionTo the filtrate was added toluene (ca.20 ml)
  4. washthe organic layer was washed with water (×2), brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customto give crude product
  8. customThe crude product was purified by column chromatography on silica gel (ca. 250 g) with hexane-ethyl acetate (3:1)

출처 및 근거

ORD 기록
ord-3d87703534534ac79b1c658d8d9a11bc
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08134004B2

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