Propargyl alcohol → 3-(3-Fluoro-5chloro-6-(1-hydroxy-2-propyn-3-yl)-2-pyridyl)4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole

HRID 1532582ノート

反応式

HRID 1532582 の反応式
[F:1][C:2]1[C:3]([C:10]2[C:14]([Cl:15])=[C:13]([O:16][CH:17]([F:19])[F:18])[N:12]([CH3:20])[N:11]=2)=[N:4][C:5](Cl)=[C:6]([Cl:8])[CH:7]=1.[CH2:21]([OH:24])[C:22]#[CH:23]>C(N(CC)CC)C>[F:1][C:2]1[C:3]([C:10]2[C:14]([Cl:15])=[C:13]([O:16][CH:17]([F:19])[F:18])[N:12]([CH3:20])[N:11]=2)=[N:4][C:5]([C:23]#[C:22][CH2:21][OH:24])=[C:6]([Cl:8])[CH:7]=1

参加物

4

反応物 2

HCID 7859Propargyl alcoholHCID 21712133HCID 21712133、化合物

生成物 1

HCID 220135743-(3-Fluoro-5chloro-6-(1-hydroxy-2-propyn-3-yl)-2-pyridyl)4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

反応条件

温度
67 °C

実験手順

2.0 of 3-(3-fluoro-5,6-dichloro-2-pyridyl)-4-chloro-5difluoromethoxy-1-methyl-[1H]-pyrazole (Example H21) are initially introduced into 15 ml of triethylamine, and 0.37 ml of propargyl alcohol is added. The mixture is then evacuated and gassed with argon 3 times under a partial water pump vacuum. Thereafter, 0.03 g of copper(I) iodide and 0.12 g of bis-triphenylphosphine-palladium dichloride (PdCl2(PPH3)2) are added and the mixture is stirred overnight at 67° C. under argon. The following day, after cooling to 22° C., 0.20 ml of propargyl alcohol, 0.03 g of copper(l) iodide and 0.12 g of PdCl2(PPH3)2 are added. The mixture is then stirred at 67° C. for 6 hours. After cooling to 22° C., ethyl acetate is added and the mixture is washed successively with dilute hydrochloric acid, water and brine. After drying over sodium sulfate, filtration and concentration in vacuo, the residue is purified over a silica gel flash column (eluting agent: n-hexane/ethyl acetate 1/1). 0.97 g of the desired title compound is obtained as a yellow oil which gradually crystallizes; melting point 92-94° C.

後処理

  1. additionis added
  2. customThe mixture is then evacuated
  3. additionThereafter, 0.03 g of copper(I) iodide and 0.12 g of bis-triphenylphosphine-palladium dichloride (PdCl2(PPH3)2) are added
  4. temperatureThe following day, after cooling to 22° C.
  5. addition0.20 ml of propargyl alcohol, 0.03 g of copper(l) iodide and 0.12 g of PdCl2(PPH3)2 are added
  6. stirringThe mixture is then stirred at 67° C. for 6 hours
  7. temperatureAfter cooling to 22° C.
  8. additionethyl acetate is added
  9. washthe mixture is washed successively with dilute hydrochloric acid, water and brine
  10. dry with materialAfter drying over sodium sulfate, filtration and concentration in vacuo
  11. customthe residue is purified over a silica gel flash column (eluting agent: n-hexane/ethyl acetate 1/1)

出典と根拠

ORDレコード
ord-95c9cab875d7484abf99bc0e38c28d3a
出典データセット
uspto-grants-2001_03
特許番号
US06204221B1

反応ノート

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