US 12,410,131 B2
Method for preparation of trans-n-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-propanone as intermediate of halofuginone
Yu Feng, Jiaxing (CN); Hong Xu, Jiaxing (CN); Jiaxuan Wu, Jiaxing (CN); Danhui Song, Jiaxing (CN); Weihui Zhong, Jiaxing (CN); Fei Ling, Jiaxing (CN); and Chao Xu, Jiaxing (CN)
Assigned to CHENGDA PHARMACEUTICALS CO., LTD., Jiaxing (CN)
Filed by CHENGDA PHARMACEUTICALS CO., LTD., Jiaxing (CN)
Filed on Dec. 14, 2022, as Appl. No. 18/065,636.
Application 18/065,636 is a continuation of application No. PCT/CN2022/086077, filed on Apr. 11, 2022.
Claims priority of application No. 202111228375.X (CN), filed on Oct. 21, 2021.
Prior Publication US 2023/0192614 A1, Jun. 22, 2023
Int. Cl. C07D 211/42 (2006.01); C07D 211/02 (2006.01)
CPC C07D 211/42 (2013.01) [C07D 211/02 (2013.01); C07B 2200/07 (2013.01)] 10 Claims
 
1. A method for the preparation of trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-propanone as an intermediate of halofuginone, characterized in that the synthetic route thereof is as follows:

OG Complex Work Unit Chemistry
and the synthesis method comprises the following steps:
(1) subjecting amino-substituted pentanal as shown in Formula IV with a thiazolyl sulfoxide compound as shown in Formula III in the presence of a base to a Mislow-Evans rearrangement reaction to obtain α,β-unsaturated ketone as shown in Formula II; and
(2) obtaining trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-propanone as shown in Formula I under the catalysis of Lewis acid with the following synthetic route:

OG Complex Work Unit Chemistry