| Popis: |
An unexpected acetyl migration is found in the product of Staudinger reduction to prepare the 4(R)-epimer of zanamivir and laninamivir octanoate as the impurity of drug substance. The synthesis and 1H NMR data assignment of (3 R,4R) or (3 R,4S)-3-acetamido-4-amino-3,4-dihydro-2H-pyran-6-carboxylates and the acetyl-migrated isomers (3 R,4R)- 3-amino-4-acetamido-3,4-dihydro-2H-pyran-6-carboxylates are herein described. Additionally, the experiments show that the acetyl migration tends to occur under neutral or acidic conditions, but not under alkalic conditions. Some organic bases are screened to block the migration during the Staudinger reduction, and the best (DBU) is identified. |
