Nitrogen → 3-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)4-hydroxy-phenyl]-acrylic acid tert-butyl ester

HRID 1181051ノート

反応式

HRID 1181051 の反応式
Br[C:2]1[CH:19]=[CH:18][C:17]([O:20][Si](C(C)(C)C)(C)C)=[CH:16][C:3]=1[CH2:4][N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15].C(#N)CC.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C.N#N.[C:65]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])(=[O:68])[CH:66]=[CH2:67].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:70]([O:69][C:65](=[O:68])[CH:66]=[CH:67][C:2]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:3]=1[CH2:4][N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15])([CH3:73])([CH3:72])[CH3:71]

参加物

9

反応物 7

HCID 947NitrogenHCID 7854PropionitrileHCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium Fluoride2 回HCID 179843932-[2-Bromo-5-(tert-butyl-dimethyl-silanyloxy)-benzyl]-isoindole-1,3-dione

生成物 1

HCID 687431663-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)4-hydroxy-phenyl]-acrylic acid tert-butyl ester収率 87%

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
95 °C

実験手順

A 12 L flask was charged with 2-[2-bromo-5-(tert-butyl-dimethyl-silanyloxy)-benzyl]-isoindole-1,3-dione (461 g, 1.03 mol), propionitrile (7 L), tri-ortho-tolyl phosphine (76.0 g, 0.250 mol) and diisopropyl ethyl amine (365 mL, 2.10 mol). The reaction mixture was degassed/purged with N2 (3×), and tert-butyl acrylate (465 mL, 3.17 mol) was added. After degassing/purging one time, palladium (II) acetate (28.0 g, 0.125 mol) was added. The stirred mixture was degassed/purged with N2 three times and heated to 95° C. for 20 h. The mixture was filtered through a hyflo cake, washed with acetonitrile, and concentrated to a brown oil (841 g). The residue was dissolved in THF (3.5 L), and tetrabutylammonium fluoride (TBAF, 650 mL, 0.65 mol, 1M in THF) was added. After 1 h, additional TBAF (95 mL) was added. The mixture was rotated on the rotary evaporator for 10 min and was concentrated to crude product (987 g). This material was purified by silica gel chromatography (toluene/ethyl acetate, 100/0 to 75/25) to give the title compound (340 g, 86.8%).

後処理

  1. additionwas added
  2. additionwas added
  3. customThe stirred mixture was degassed/purged with N2 three times
  4. filtrationThe mixture was filtered through a hyflo cake
  5. washwashed with acetonitrile
  6. concentrationconcentrated to a brown oil (841 g)
  7. dissolutionThe residue was dissolved in THF (3.5 L)
  8. customThe mixture was rotated on the rotary evaporator for 10 min
  9. concentrationwas concentrated to crude product (987 g)
  10. customThis material was purified by silica gel chromatography (toluene/ethyl acetate, 100/0 to 75/25)

出典と根拠

ORDレコード
ord-439de2b55acf4ab4a8cd76b5c1cba243
出典データセット
uspto-grants-2007_10
特許番号
US07282501B2

反応ノート

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