Sodium Hydroxide → (-)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid [2-(N-methyl-N-phenylmethylamino)ethyl]ester

Participants

Reaction Conditions

Reaction Steps

6.29 g oxalyl chloride in 73 mL ethyl acetate are added to a solution of 11.3 mL absolute dimethylformamide in 220 mL absolute ethyl acetate cooled to 0° C., followed by stirring for 15 minutes at 0° to 5° C. After adding of 12.8 g (-)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid there are added dropwise 3.9 g pyridine, dissolved in 73 mL ethyl acetate and the mixture is stirred for 60 minutes at 0° C. After adding of 10.26 g 2-(N-benzyl-N-methylamino)-ethanol, dissolved in 3.03 g pyridine and 146 mL methylene chloride the mixture is stirred for 1 hour at 5° to 10° C. The reaction mixture is subsequently stirred with 3×140 mL water and 2×140 mL 1N sodium hydroxide. The organic phase is separated off, dried over sodium sulfate and evaporated to dryness. The oily residue is purified over silica gel with toluene:ethyl acetate (7:3) as elution agent. After distilling off the elution agent there is obtained an oily product. The oil is dissolved with 2.52 g fumaric acid in 350 mL ethyl acetate under heating to reflux temperature. After filtration the reaction mixture is evaporated to about 50 mL. The precipitated product is filtered off with suction, dispersed in 10 mL toluene and stirred with 5 mL 1M aqueous ammonium hydroxide solution. The toluene phase is washed with 2×5 mL of water. The organic phase is after drying over sodium sulfate evaporated to dryness. There is obtained an oily product, yield 5.3 g (32% of theory); [α]D =-40.8° (c=1/dichloromethane).

Provenance & Evidence