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 1087049Notes

Reaction equation

HRID 1087049 reaction equation
[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

Participants

9

Reactant 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

Product 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-enoateYield 102%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-cd2091a2d3424ebba3eb6919e694075e
Source dataset
uspto-grants-1991_07
Patent number
US05034399

Reaction notes

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