反应详情

温度

50 °C

In 500 mL of methanol-water (volume ratio 1:1) was suspended 50.6 g of a racemic mixture, 1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (content 98.8%; trans compound 90.2%, cis compound 9.6%). To the suspension was added 25 mL of triethylamine, which was made into a solution by heating (50° C.). To the solution was added 13.6 g (0.5 equivalent) of (1R,2S)-norephedrine. The mixture was once made into a solution, which was crystallized in about 10 minutes, followed by cooling to 30° C. over about 60 minutes, and then to 5° C. The crystals were aged for 60 minutes at the same temperature. The resulting crystals were collected by filtration, washed with 200 mL of cold methanol-water (volume ratio 1:1) and dried at 35° C. under reduced pressure to afford 29.9 g of substantially pure (2R,4S)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid.(1R,2S)-norephedrine salt as colorless crystals [HPLC area percentage: (2R,4R):(2S,4S):(2S,4R):(2R,4S)=0.86%:0.46%:0.50%:97.9%].

1. customwas crystallized in about 10 minutes
2. temperatureby cooling to 30° C. over about 60 minutes
3. customto 5° C
4. filtrationThe resulting crystals were collected by filtration
5. washwashed with 200 mL of cold methanol-water (volume ratio 1:1)
6. customdried at 35° C. under reduced pressure