p-Toluenesulfonic acid → HCID 24803256, compound

Participants

Reaction Conditions

Reaction Steps

Dissolve (R)-3-(4-{[5-(4-chloro-phenyl)-3-methyl-thiophene-2-carbonyl]-amino}-2-methoxy-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (2.63 g, 4.72 mmol) in tetrahydrofuran (35 mL) under argon and cool to −78° C. Add 1.7 M tert-butyllithium in pentane (6.1 mL, 10.38 mmol) while maintaining the temperature below −70° C. Stir the solution at −78° C. for 20 min. Add N,N-dimethylformamide (2.68 mL, 34.46 mmol) to the solution maintaining temperature below −70° C. Remove the cooling bath after 5 min and stir the reaction for 30 min. Quench the reaction with saturated aqueous ammonium chloride (20 mL). Dilute the mixture with water (10 mL) and extract with ethyl acetate (3×30 mL). Dry the combined organics (Na2SO4), filter, and concentrate in vacuo. Dissolve the residue in 30 mL of ethyl acetate and add p-toluenesulfonic acid (1.41 g, 7.08 mmol). Heat the mixture at reflux overnight, cool, and dilute with water (30 mL). Make the mixture basic with 1 N NaOH and extract with ethyl acetate (3×40 mL). Dry the combined organics (Na2SO4), filter, and concentrate in vacuo. Purify by chromatography (dichloromethane to 7% 2 M ammonia in methanol/dichloromethane) to afford 0.77 g (35%) of 2-(4-chloro-phenyl)-6-[3-methoxy-4-((R)-piperidin-3-yloxy)-phenyl]-6H-thieno[2,3-c]pyridine-7-one.

Provenance & Evidence