1-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine → 4-[2-(5-Benzylcarbamoyl-6-chloro-2-methylsulfanylpyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 4,6-dichloro-2-methylsulfanylpyrimidine-5-carboxylic acid benzylamide (3 mmol) in THF (20 mL) is added KOtBu (3.6 mmol) at 0° C. under N2. After stirred at 0° C. for 20 min, the above mixture is added dropwise to a solution of 4-(2-hydroxyethyl)piperidine-1-carboxylic acid tert-butyl ester (3.3 mmol) in THF (20 mL) at −78° C. The resulting mixture is gradually warm up to −30° C. over 2.5 h. The reaction is quenched by the addition of H2O. The mixture is extracted twice with AcOEt. The organic layer is dried over Na2SO4, filtered, and concentrated to give 4-[2-(5-benzylcarbamoyl-6-chloro-2-methylsulfanylpyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester as a white solid; 1H-NMR (CDCl3), δ 1.07-1.17 (2H, m), 1.48 (9H, s), 1.62-1.70 (2H, m), 2.54 (3H, s), 2.64 (2H, br t), 4.06 (2H, m), 4.45 (2H, t), 4.64 (2H, d), 6.06 (1H, t), 7.30-7.34 (2H, m), 7.35-7.36 (3H, m).

Provenance & Evidence