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

HRID 422732ノート

反応式

HRID 422732 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
108 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-69f05b6bd9b5491489f08fa6a33e5da0
出典データセット
uspto-grants-2012_01
特許番号
US08101613B2

反応ノート

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