Potassium Carbonate → 7-Chloro-8-fluoro-4-methyl-2-phenylquinoline

HRID 244222노트

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HRID 244222 반응식
Br[C:2]1[C:11]2[C:6](=[C:7]([F:13])[C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:3]=1.[CH3:20]B(O)O.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C(OCC)(=O)C.O.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>[Cl:12][C:8]1[C:7]([F:13])=[C:6]2[C:11]([C:2]([CH3:20])=[CH:3][C:4]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:5]2)=[CH:10][CH:9]=1

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 139377Methylboronic AcidHCID 576810164-Bromo-7-chloro-8-fluoro-2-phenylquinoline

생성물 1

HCID 576810927-Chloro-8-fluoro-4-methyl-2-phenylquinoline

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
108 °C

실험 절차

4-Bromo-7-chloro-8-fluoro-2-phenylquinoline (1.1 g, 03.3 mmol), methane boronic acid (196 mg, 3.27 mmol), potassium carbonate (1.4 g, 9.8 mmol) and 1,4-dioxane (4 mL) were combined and stirred in a 10 mL R.B. flask. The flask was subjected to 3 vacuum-argon cycles. Tetrakis(triphenylphosphine)palladium(0) (380 mg, 0.33 mmol) was added, and the reaction was again subjected to 3 vacuum argon-cycles. The reaction was heated at 108° C. (external temperature) for 27 h, at which point the reaction was allowed to cool, and was diluted with ethyl acetate (30 mL), and water (30 mL). The layers were separated, and the aqueous layer extracted with ethyl acetate (30 mL). The organics were combined, dried over sodium carbonate, and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with hexanes:methylene chloride 2:1. This afforded the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 2.75 (s, 3H), 7.47-7.55 (m, 4H), 7.69-7.72 (dd, 1H, J=8.9 & 1.6 Hz), 7.77 (s, 1H), 8.18-8.21 (m, 2H); MS (APCI+): 272.07 (100) [MH+], 274.03 (30) [(M+2)H+]; HPLC tR=3.80 min (OpenLynx, nonpolar—5 min).

후처리

  1. temperatureto cool
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with ethyl acetate (30 mL)
  4. dry with materialdried over sodium carbonate
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel
  7. washeluting with hexanes:methylene chloride 2:1

출처 및 근거

ORD 기록
ord-73b20b0314cf4bdaac105bda5cb07867
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653268B2

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