[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13]([CH2:16]Cl)=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.C([O-])(O)=O.[Na+]>C(#N)C.O.C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13]([CH2:16][N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]Add 3-(tert-butoxycarbonylamino-methyl)-6-chloromethyl-pyridine (500 mg, 1.95 mmol) to a solution of piperidine (0.58 mL, 5.84 mmol) and saturated aqueous NaHCO3 (2.5 mL) in acetonitrile (15 mL). Stir the mixture at room temperature overnight. Dilute the mixture with water (20 mL) and DCM (25 mL), separate the layers and extract the aqueous layer with DCM (3×20 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (80 g pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 1:1 gradient over 60 min, 80 mL/min) to obtain the desired intermediate as a colorless oil (547 mg, 92%). MS (APCI+) m/z: 306 (M+H)+.
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