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

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Reaction Steps

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.

Provenance & Evidence