Yield:318280-69-2 11%

Reaction Conditions:

with lithium hydroxide monohydrate in tetrahydrofuran;methanol;lithium hydroxide monohydrate at 0 - 20; for 6.5 h;

Steps:

Synthesis of 1-(2-chloroacetyl)piperidine-4-carboxylic acid (13) and 1-(2-chloroacetyl)piperidine-3-carboxylic acid (15):

General procedure: The corresponding ethyl ester (1 equiv.) was dissolved in a mixture of tetrahydrofuran, water, and methanol (1:1:1) and cooled to 0-4°C on an ice bath. Lithium hydroxide (1.5 equiv.) was added and stirred for 30min. The reaction was brought to room temperature and stirred further for 6h. The volatiles were removed under reduced pressure. The remaining aqueous layer was acidified with 1M hydrochloric acid and washed with EtOAc. The resulting aqueous layer was evaporated under reduced pressure.

References:

Grabrijan, Katarina;Hrast, Martina;Proj, Matic;Dol?ak, Ana;Zdovc, Irena;Imre, Tímea;Petri, László;ábrányi-Balogh, Péter;Keser?, Gy?rgy M.;Gobec, Stanislav [European Journal of Medicinal Chemistry,2022,vol. 243,art. no. 114752]