Cesium carbonate → (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one

HRID 1754938노트

반응식

HRID 1754938 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[CH3:9].[OH:10][C@H:11]1[CH2:15][NH:14][C:13](=[O:16])[CH2:12]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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.C(Cl)(Cl)Cl.[Pd].[Pd].O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:14]2[CH2:15][C@H:11]([OH:10])[CH2:12][C:13]2=[O:16])=[CH:4][C:3]=1[CH3:9]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 185505(R)-(+)-4-Hydroxy-2-pyrrolidinoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27355742-Bromo-5-iodotoluene

생성물 1

HCID 66816684(R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one수율 38.1%

시약·촉매·용매 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
110 °C

실험 절차

A mixture of 2-bromo-5-iodotoluene (500 mg, 1.68 mmol), (R)-4-hydroxy-pyrrolidinone (204 mg, 2.02 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (58.5 mg, 0.101 mmol), tris(dibenzylideneacetone)-dipalladium(0)-chloroform adduct (35.0 mg, 0.034 mmol) and cesium carbonate (769 mg, 2.36 mmol) in 1,4-dioxane (degassed, 5 ml) was stirred at 110° C. overnight in a nitrogen stream. The reaction mixture was treated with H2O and extracted with AcOEt (×2). The organic layers were combined and sequentially washed with H2O and saturated brine, and then dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (n-hexane/AcOEt) to give (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one as a pale brown solid (173 mg, 38%).

후처리

  1. extractionextracted with AcOEt (×2)
  2. washsequentially washed with H2O and saturated brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (n-hexane/AcOEt)

출처 및 근거

ORD 기록
ord-83cc438b785f4e858558a55f309b7fb2
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169254B2

반응 노트

불러오는 중…