Synthetic Communications ( IF 1.8 ) Pub Date : 2021-08-16 , DOI: 10.1080/00397911.2021.1966038 Chuanqi Duan 1 , Weiyuan Liu 1 , Liang Chen 1 , Jing Pan 1 , Yubin Liu 1 , Kuaile Lin 1 , Weicheng Zhou 1
Abstract
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.
中文翻译:
3-acetamido-4-amino-3,4-dihydro-2H-pyran-6-carboxylates 及其乙酰基迁移异构体的合成和 1H NMR 数据归属
摘要
在施陶丁格还原制备扎那米韦的4( R )-差向异构体和辛酸拉尼米韦作为原料药杂质的产物中发现了意想不到的乙酰基迁移。(3 R,4R)或(3 R,4S)- 3-acetamido-4-amino-3,4-dihydro-2 H -pyran-6-carboxylates 和乙酰基迁移的合成和1 H NMR 数据归属异构体(3R,4R) - 3-氨基-4-乙酰氨基-3,4-二氢-2 ħ吡喃-6-羧酸酯在本文中描述。此外,实验表明乙酰迁移倾向于在中性或酸性条件下发生,但在碱性条件下不会发生。筛选一些有机碱以阻止迁移过程中的迁移Staudinger减少,并确定最佳 (DBU)。