TY - JOUR
T1 - Fast and Efficient Synthesis of Racemic Baloxavir Catalyzed by Strong Solid Acid under Microwave Conditions
AU - Wang, Yiyun
AU - Lv, Xiaofang
AU - Meng, Zihui
AU - Xu, Zhibin
AU - Zheng, Zhonghui
AU - Li, Jiarong
AU - Xue, Min
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7
Y1 - 2022/7
N2 - The compound (±)-12aR-12-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-7-hydroxy-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione is the intermediate of baloxavir marboxil. In the literature, traditional heating methods and common acid catalysts are used, which result in long reaction times and a low yield. Therefore, finding an efficient and environmentally friendly synthetic route is necessary. In this study, (±)-12aR-12-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-7-benzyloxy-3,4,12,12a-tetrahydro-1h-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione (compound 3) was synthesized using a sulfonate resin solid acid catalyst (HND-580) under microwave conditions. The benzyl group was removed without further purifi-cation, and an intermediate, racemic baloxavir, was obtained under microwave irradiation. The total yield of the two steps was 78%. This method greatly reduces the reaction time and improves production efficiency.
AB - The compound (±)-12aR-12-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-7-hydroxy-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione is the intermediate of baloxavir marboxil. In the literature, traditional heating methods and common acid catalysts are used, which result in long reaction times and a low yield. Therefore, finding an efficient and environmentally friendly synthetic route is necessary. In this study, (±)-12aR-12-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-7-benzyloxy-3,4,12,12a-tetrahydro-1h-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione (compound 3) was synthesized using a sulfonate resin solid acid catalyst (HND-580) under microwave conditions. The benzyl group was removed without further purifi-cation, and an intermediate, racemic baloxavir, was obtained under microwave irradiation. The total yield of the two steps was 78%. This method greatly reduces the reaction time and improves production efficiency.
KW - baloxavir marboxil
KW - intermediate
KW - microwave irradiation
KW - sulfonate resin solid acid
KW - synthesis
UR - http://www.scopus.com/inward/record.url?scp=85133127603&partnerID=8YFLogxK
U2 - 10.3390/cryst12070891
DO - 10.3390/cryst12070891
M3 - Article
AN - SCOPUS:85133127603
SN - 2073-4352
VL - 12
JO - Crystals
JF - Crystals
IS - 7
M1 - 891
ER -