tert-butyl 2-[[(2-chloroacetyl)amino]methyl]piperidine-1-carboxylate

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl 2-((2-chloroacetamido)methyl)piperidine-1-carboxylate (590 mg, 2.02 mmol) and POCl3 (5 mL) was stirred at room temperature for 30 min. Then 2-amino-4-bromobenzoic acid (442 mg, 1.94 mmol) was added to the mixture and stirred for another 20 min. After warming slowly to 100° C., the mixture was maintained at 100° C. for 1.5 h. Then the reaction mixture was poured into ice water, adjusted pH to 8 and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine and dried over Na2SO4. After filtration and concentration, the crude product was directly used for the next reaction. MS (ESI): 370, 372 (MH+). the mixture was maintained at 100° C. for 1.5 h extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with brine dried over Na2SO4 After filtration and concentration the crude product was directly used for the next reaction

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 2-(aminomethyl)piperidine-1-carboxylate (2.0 g, 9.3 mmol) and diisopropylethylamine (5 mL) in DCM (30 mL) was added 2-chloroacetyl chloride (1.2 g, 10.6 mmol) dropwise at 0° C. The mixture was stirred at room temperature overnight. Then the mixture was quenched with water (30 mL) and extracted with DCM (5×100 mL). The combined organic layers were dried over Na2SO4. After filtration and concentration, the residue was used directly for the next reaction. MS (ESI): 291, 293 (MH+). Then the mixture was quenched with water (30 mL) extracted with DCM (5×100 mL) The combined organic layers were dried over Na2SO4 After filtration and concentration the residue was used directly for the next reaction