Methyl acetoacetate → methyl-(E)-7[5-(4-fluorophenyl)1,2-dihydro-7-isopropyl-2-oxo-1,8-naphthyridin-6-yl]-5-hydroxy-3-oxo-hept-6-enoate

HRID 1087049노트

반응식

HRID 1087049 반응식
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:32](/[CH:33]=[CH:34]/[CH:35]=[O:36])=[C:31]([CH:37]([CH3:39])[CH3:38])[N:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][C:27](=[O:40])[NH:28]3)=[CH:19][CH:18]=1>O1CCCC1.CCCCCC.O.C(O)(=O)C>[CH3:8][O:7][C:1](=[O:6])[CH2:2][C:3](=[O:4])[CH2:5][CH:35]([OH:36])/[CH:34]=[CH:33]/[C:32]1[C:23]([C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)=[C:24]2[C:29](=[N:30][C:31]=1[CH:37]([CH3:39])[CH3:38])[NH:28][C:27](=[O:40])[CH:26]=[CH:25]2

참가 물질

9

반응물 4

HCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 14850559(E)-3-[5-(4-Fluorophenyl)-1,2-dihydro-7-isopropyl-2-oxo1, 8-naphthyridin-6-yl]-prop-2-enalHCID 178418339Butyllithium

생성물 1

HCID 14850560methyl-(E)-7[5-(4-fluorophenyl)1,2-dihydro-7-isopropyl-2-oxo-1,8-naphthyridin-6-yl]-5-hydroxy-3-oxo-hept-6-enoate수율 102%

시약·촉매·용매 4

HCID 176Acetic Acid용매HCID 962Water용매HCID 8028Tetrahydrofuran용매3회HCID 8058Hexane용매

실험 절차

5.47 g (50.7 mmol) of methyl acetoacetate in 5 ml of tetrahydrofuran are added dropwise at -5° C. to 0° C. under argon to a suspension of 1.69 g (56.4 mmol) of 80% strength sodium hydride in 50 ml of anhydrous tetrahydrofuran. After 15 min, 41 ml (67.6 mmol) of 15% strength butyl lithium in hexane are added dropwise at the same temperature and, after a further 15 min, a solution of 5.68 g (16.9 mmol) of the compound from Example 5 in 150 ml of tetrahydrofuran. The mixture is stirred at room temperature for one hour, then 11.2 g of acetic acid in 120 ml of water are cautiously added dropwise and the mixture is extracted three times with ethyl acetate. The organic phases are washed with saturated sodium hydrogen carbonate and sodium chloride solution, dried over sodium sulphate and concentrated. 7.8 g of crude methyl-(E)-7[5-(4 -fluorophenyl)1,2-dihydro-7-isopropyl-2-oxo-1,8-naphthyridin-6-yl]-5-hydroxy-3-oxo-hept-6-enoate are obtained as orange oil.

후처리

  1. extractionthe mixture is extracted three times with ethyl acetate
  2. washThe organic phases are washed with saturated sodium hydrogen carbonate and sodium chloride solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated

출처 및 근거

ORD 기록
ord-cd2091a2d3424ebba3eb6919e694075e
출처 데이터셋
uspto-grants-1991_07
특허 번호
US05034399

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