Methyl Acrylate → (S)-2-[4-((E)-2-methoxycarbonyl-vinyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1802743ノート

反応式

HRID 1802743 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]1[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C1CCCCC1)C1CCCCC1.[C:34]([O:38][CH3:39])(=[O:37])[CH:35]=[CH2:36]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]1[CH:18]=[CH:17][C:16](/[CH:36]=[CH:35]/[C:34]([O:38][CH3:39])=[O:37])=[CH:15][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 7294Methyl AcrylateHCID 24210N-Methyl dicyclohexylamineHCID 57899258(s)-Tert-butyl 2-(4-bromophenyl)pyrrolidine-1-carboxylate

生成物 1

HCID 57899218(S)-2-[4-((E)-2-methoxycarbonyl-vinyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester収率 99%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

To a degassed solution of (S)-2-(4-bromo-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (44.0 g, 128 mmol) in 1,4-dioxane (500 mL) in a sealed pressure vessel was sequentially added N-methyldicyclohexylamine (32.9 mL, 154 mmol), (t-Bu)3HBF4 (1.19 g, 4.10 mmol), methyl acrylate (34.8 mL, 385 mmol) and Pd2(dba)3 (1.19 g, 1.29 mmol). The reaction mixture was heated to 150° C. in a sealed pressure vessel for 4.5 h then cooled in ice bath and placed in refrigerator for 16 h. The reaction mixture was filtered through a Celite pad, the filter cake was washed with 250 mL ethyl acetate, and the combined organics were concentrated in vacuo to a yellow oil. The oil was taken up in 20% ethyl acetate in heptane, sonicated and filtered, and the filtrate was concentrated again in vacuo. The residue was dissolved in ethyl acetate and the organic solution was washed sequentially with 10% citric acid, sodium bicarbonate solution and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel column chromatography (ethyl acetate/heptane) or recrystallized from 20% ethyl acetate in heptane. Total recovery is 42.1 g (99% yield).

後処理

  1. temperaturethen cooled in ice bath
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. washthe filter cake was washed with 250 mL ethyl acetate
  4. concentrationthe combined organics were concentrated in vacuo to a yellow oil
  5. customsonicated
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated again in vacuo
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. washthe organic solution was washed sequentially with 10% citric acid, sodium bicarbonate solution and saturated sodium chloride solution
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified via silica gel column chromatography (ethyl acetate/heptane)
  14. customrecrystallized from 20% ethyl acetate in heptane

出典と根拠

ORDレコード
ord-89bf67fed98a4a99abe5b6a6aaf8be06
出典データセット
uspto-grants-2013_01
特許番号
US08349883B2

反応ノート

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