Triphenylphosphine → HCID 86685699、化合物

HRID 1053996ノート

反応式

HRID 1053996 の反応式
[CH3:1][O:2][C:3](=[O:27])[CH2:4][CH2:5][C:6]1[CH:10]=[C:9]([CH3:11])[N:8]([CH2:12][C:13]2[CH:18]=[C:17](Br)[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[N:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:47][Si:48]([C:51]#[CH:52])([CH3:50])[CH3:49]>CN(C=O)C.[Cu]I>[CH3:1][O:2][C:3](=[O:27])[CH2:4][CH2:5][C:6]1[CH:10]=[C:9]([CH3:11])[N:8]([CH2:12][C:13]2[CH:18]=[C:17]([C:52]#[C:51][Si:48]([CH3:50])([CH3:49])[CH3:47])[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[N:7]=1

参加物

6

反応物 3

HCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 86685698HCID 86685698、化合物

生成物 1

HCID 86685699HCID 86685699、化合物収率 48.4%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

A mixture of 3-{1-[5-Bromo-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-3-yl}-propionic acid methyl ester (0.0774 g, 0.18 mmol), [PdCl2(PPh3)]2 (0.007 g, 0.01 mmol), PPh3 (0.0094 g, 0.018 mmol) mmol), CuI (2 mg, 0.01 mmol), trimethylsilylacetylene (0.0196 g, 0.2 mmol), Et2N (0.07314 g, 2.72 mmol in DMF (1 ml) heated at 120° C. in a microwave reactor under a N2 atmosphere for 50 min. The mixture was partitioned between 0.1 M HCl and EtOAc. The organic layer was washed with brine, dried (MgSO4) and evaporated to dryness. The residue was purified by MPLC (20 g SiO2 cartridge, eluent 90% iso-hexane-10% EtOAc) yielding 3-{1-[5-trimethylsilanylethynyl-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-3-yl}-propionic acid methyl ester (0.0396 g). This was dissolved in THF (20 ml), MeOH (20 ml), glacial acetic acid (8 ml) and Bu4NF solution (24 ml, 1M) was added. The mixture was stirred at RT overnight then heated at 60° C. for 3 hours, thereafter cooled to RT and partitioned between sat. NH4Cl solution and EtOAc, the organic layer was washed with brine, dried (MgSO4) and evaporated to dryness. The residue was purified by MPLC (20 g SiO2 cartridge, eluent 85% iso-hexane-15% EtOAc) yielding 3-{1-[5-Ethynyl-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-3-yl}-propionic acid methyl ester (0.0078 g) which was converted to the title compound following the method in Example 1, Step 8.

後処理

  1. customThe mixture was partitioned between 0.1 M HCl and EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. customevaporated to dryness
  5. customThe residue was purified by MPLC (20 g SiO2 cartridge, eluent 90% iso-hexane-10% EtOAc)

出典と根拠

ORDレコード
ord-b98f260513e24312aa803d421dc7b08d
出典データセット
uspto-grants-2016_07
特許番号
US09394284B2

反応ノート

読み込み中…