	US 12,227,478 B2
	Processes for preparing (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine or a salt thereof and processes for preparing tofacitinib using the same
Sang-Ho Oh, Gunpo-si (KR); Doo-Byung Lee, Yongin-si (KR); Kyoung-Chan Kwon, Hwaseong-si (KR); Sang-Won Kim, Hwaseong-si (KR); Hyo-Ick Hwang, Suwon-si (KR); Kyeong-Sill Lee, Hwaseong-si (KR); Ik-Su Jo, Osan-si (KR); Ji-Hye Choi, Suwon-si (KR); Sung-Hee Cho, Suwon-si (KR); and Su-Young Lee, Hwaseong-si (KR)
Assigned to YUHAN CORPORATION, Seoul (KR)
Appl. No. 17/594,062
Filed by YUHAN CORPORATION, Seoul (KR)
PCT Filed Apr. 3, 2020, PCT No. PCT/KR2020/004547 § 371(c)(1), (2) Date Sep. 30, 2021, PCT Pub. No. WO2020/204647, PCT Pub. Date Oct. 8, 2020.
Claims priority of application No. 10-2019-0040383 (KR), filed on Apr. 5, 2019.
Prior Publication US 2022/0144774 A1, May 12, 2022
Int. Cl. C07D 211/56 (2006.01); C07D 487/04 (2006.01)

CPC C07D 211/56 (2013.01) [C07D 487/04 (2013.01)]

10 Claims

1. A process for preparing (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine acetate, the process of which comprises:

(a) reacting racemic methyl (1-benzyl-4-methylpiperidin-3-yl) carbamate and dibenzoyl-L-tartaric acid by heating under reflux in a solvent selected from the group consisting of isopropanol, an aqueous solution of isopropanol, and a mixed solvent of isopropanol and an organic solvent, followed by cooling to prepare isopropanol solvate of methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl) carbamate dibenzoyl-L-tartrate; and

(b) reacting the isopropanol solvate of methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl) carbamate dibenzoyl-L-tartrate prepared in Step (a) with a base to convert to methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl) carbamate; reducing the methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl) carbamate to prepare (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine; and then reacting the (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine with acetic acid to prepare (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine acetate.