[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][NH2:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:14][C:15]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:16]=1[CH:17]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][NH:13][CH2:17][C:16]2[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:15]=2[Cl:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]To a solution of 3-aminomethyl-azetidine-1-carboxylic acid tert-butyl ester (300 mg, 1.6 mmol), 2,4-dichlorobenzaldehyde (281 mg, 1.61 mmol) and acetic acid (0.09 mL, 1.61 mmol) in 1,2-dichloroethane (16 mL) at 0° C. is added sodium triacetoxy-borohydride (476 mg, 2.25 mmol). The reaction is warmed to ambient temperature and stirred overnight under N2. The reaction mixture is poured on to 2N NaOH (20 mL) and extracted with ethyl acetate (3×). The combined organic extracts are washed with aqueous saturated NaCl, dried (Na2SO4), filtered and concentrated. The crude product is purified by flash chromatography on silica gel eluting with 5% EtOH (10% NH4OH)/chloroform to yield 360 mg (65%) of 3-[(2,4-dichlorobenzylamino)-methyl]-azetidine-1-carboxylic acid tert-butyl ester. 1H NMR (400 MHz, CD3OD) δH: 7.49-7.47 (2H, m), 7.36-7.34 (1H, m), 4.05-4.01 (2H, m), 3.88 (2H, s), 3.64-3.61 (2H, m), 2.8 (2H, m), 2.78-2.74 (1H, m), 1.46 (9H, s). Mass spectrum (ion spray): m/z=345.1 (M+H).
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