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

HRID 422732노트

반응식

HRID 422732 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

반응 조건

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-69f05b6bd9b5491489f08fa6a33e5da0
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101613B2

반응 노트

불러오는 중…