Phosphate → 6-cyano-2,2-dimethyl-4-{1,2-dihydro-2-oxo-4-(1-hydroxy-2-ethoxycarbonylethyl)-1-pyridinyl}-2H-benzo[b]pyran

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Reaction Conditions

Reaction Steps

In 40 ml of anhydrous tetrahydrofuran, is dissolved 3.64 ml of diisopropylamine. The resulting solution is cooled to 0° C. After dropping 15.4 ml of 1.62M solution of n-butyllithium in n-hexane thereto and stirring the resulting mixture for 10 minutes at that temperature, it is cooled to -78° C. and stirred for 20 minutes. Then, 2.34 ml of ethyl acetate is dropped and stirred at that temperature for 30 minutes. Then, 160 ml of an anhydrous tetrahydrofuran solution containing 6.13 g of the 6-cyano-2,2-dimethyl-4-(1,2-dihydro-2-oxo-4-formyl-1-pyridinyl)-2H-benzo[b]pyran obtained in Example 25 is added at that temperature over a period of 55 minutes, and the whole mixture is reacted first at that temperature for one hour, then at 0° C. for 30 minutes and then at room temperature for 30 minutes. After stopping the reaction by adding 0.2M phosphate buffer, the reaction mixture is extracted with ethyl acetate. The organic layer is washed successively with 2N aqueous hydrochloric acid, water and saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The inorganic matter is filtered off, and the filtrate is concentrated under reduced pressure. The residue thus obtained is purified by silica gel column chromatography using 3/1 mixture of ethyl acetate/n-hexane as a developing solvent. Thus, 5.88 g of 6-cyano-2,2-dimethyl-4-{1,2-dihydro-2-oxo-4-(1-hydroxy-2- ethoxycarbonylethyl)- 1-pyridinyl}-2H-benzo[b]pyran is obtained.

Provenance & Evidence