Triethylamine → 5-[(2-Fluorophenyl)ethynyl]-4-methyl-1,3-thiazole

HRID 967744ノート

反応式

HRID 967744 の反応式
Br[C:2]1[S:6][CH:5]=[N:4][C:3]=1[CH3:7].C(N(CC)CC)C.[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]#[CH:23]>COCCOC.C(OCC)(=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]#[C:23][C:2]1[S:6][CH:5]=[N:4][C:3]=1[CH3:7]

参加物

8

反応物 3

HCID 8471TriethylamineHCID 6433581-Ethynyl-2-fluorobenzeneHCID 150209975-Bromo-4-methyl-1,3-thiazole

生成物 1

HCID 222913245-[(2-Fluorophenyl)ethynyl]-4-methyl-1,3-thiazole収率 113.4%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

5-Bromo-4-methyl-1,3-thiazole (500 mg, 2.8 mmol) and CuI (120 mg, 0.63 mmol) were combined in DME (5 mL) and argon gas was bubbled through the suspension for several minutes to deoxygenate the mixture. Triethylamine (2.0 mL, 14 mmol) and PdCl2(PPh3)2 (220 mg, 0.32 mmol) were added, followed by the dropwise addition of (2-fluorophenyl)acetylene (1.0 g, 8.3 mmol). The reaction mixture was heated and after 3 h at reflux, allowed to cool, diluted with ethyl acetate (20 mL), and filtered through Celite™. The filter pad was washed thoroughly with ethyl acetate and the combined filtrates were washed with water (20 mL), brine (20 mL), dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography on silica gel eluting with 95:5 hexane:ethyl acetate to afford 5-[(2-fluorophenyl)ethynyl]-4-methyl-1,3-thiazole (690 mg, 56% yield) as a red oil. 1H NMR (CDCl3, 300 MHz) δ 8.65 (s, 1H), 7.53–7.47 (m, 1H), 7.36–7.26 (m, 1H), 7.17–7.09 (m, 2H), 2.62 (s, 3H). MS (ESI) 217.3 (M+).

後処理

  1. customargon gas was bubbled through the suspension for several minutes
  2. customto deoxygenate the mixture
  3. temperatureThe reaction mixture was heated and after 3 h
  4. temperatureat reflux
  5. temperatureto cool
  6. filtrationfiltered through Celite™
  7. washThe filter pad was washed thoroughly with ethyl acetate
  8. washthe combined filtrates were washed with water (20 mL), brine (20 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated in vacuo
  12. customthe residue was purified by column chromatography on silica gel eluting with 95:5 hexane

出典と根拠

ORDレコード
ord-e0ffbac1885542e98f2b6907707ff54c
出典データセット
uspto-grants-2005_10
特許番号
US06956049B1

反応ノート

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