反应详情

In 30 ml of dichloromethane was suspended 455 mg of compound (2) and after adding thereto 801 mg of HOBT and 1.059 g of DCC and stirring the mixture for 15 minutes, the reaction was maintained for 15 minutes at room temperature. The reaction mixture was ice-cooled again and then 50 ml of a dichloromethane solution of foregoing compound (11) was added to the reaction mixture. After reacting the mixture for one hour under ice-cooling, the reaction was maintained overnight at room temperature. Precipitates thus formed was filtered off and the filtrate was concentrated to dryness. The residue thus obtained was dissolved in 20 ml of water-methanol (4:1) and subjected to HP-20 column chromatography. When the eluate by water-methanol (1:4) was concentrated to dryness, 1.135 g of crude Nα -[(S)-2-azetidinone-4-carbonyl]-L-histidyl-L-proline benzyl ester (12) was obtained. When the product was subjected to silica gel column chromatography again and eluted with chloroform-methanol-aqueous ammonia (40:10:1), 827 mg of the pure product (12) was obtained.

1. additionafter adding
2. temperaturecooled again
3. customfor one hour
4. temperaturecooling
5. temperaturethe reaction was maintained overnight at room temperature
6. customPrecipitates thus
7. customformed
8. filtrationwas filtered off
9. concentrationthe filtrate was concentrated to dryness
10. customThe residue thus obtained
11. concentrationWhen the eluate by water-methanol (1:4) was concentrated to dryness