(3S)-4-Methyl-3-Morpholinecarboxylic Acid synthesis

Yield:1315051-74-1 96%

Reaction Conditions:

with formic acid in methanol; for 6 h;Reflux;

Steps:

4.1.10 (S)-4-Methylmorpholine-3-carboxylic acid (7)

To a stirred solution of carboxylic acid 6 (0.26g, 2.0mmol) in methanol (5mL) was added 40mol % formaldehyde (0.75mL, 10.0mmol) and formic acid (0.15mL, 4.0mmol) at 0°C. The reaction mixture was heated to reflux for 6h. Upon completion, the solvent was removed under reduced pressure. Water was added to the residue and extracted with ethyl acetate. The combined organic layers were removed under reduced pressure to furnish 7 as a white powder (0.28g, 96%): ¹H NMR (500MHz, CD₃OD) δ 4.25-4.21 (m, 1H), 4.01 (d, J=13.0Hz, 1H), 3.77-3.72 (m, 1H), 3.67-3.60 (m, 2H), 3.41 (d, J=13.0Hz, 1H), 3.22-3.17 (m, 1H), 2.96 (s, 3H); ¹³C NMR (101MHz, CD₃OD) δ 169.6, 68.7, 68.5, 65.0, 53.6, 43.1. LCMS (ESI) m/z: [M-H]^- 144.3.

References:

Zhu, Mei;Zhou, Huiyu;Ma, Ling;Dong, Biao;Ding, Jiwei;Zhou, Jinming;Wang, Juxian;Zhang, Guoning;Wang, Minghua;Shan, Qi;Cen, Shan;Wang, Yucheng [European Journal of Medicinal Chemistry,2022,vol. 233,art. no. 114251]