[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C@H:6]([NH2:20])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)[CH3:2].ClC([O:25][C:26]1C=CC=CC=1)=O.[N:32]1C=CC=CC=1.[OH-].[NH4+]>C1COCC1.CS(C)=O>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C@H:6]([NH:20][C:26]([NH2:32])=[O:25])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:12][CH:13]=1)[CH3:2]To a suspension of (R)-3-amino-4-biphenyl-4-yl-butyric acid ethyl ester (200 mg, 0.625 mmol) in THF (10 ml) at 0° C. was added phenyl chloroformate (0.087 ml, 0.688 mmol) and pyridine (0.126 ml, 1.563 mmol). The mixture is stirred at 0° C. for 5 min then is warmed up to room temperature. LCMS monitored the reaction until it is complete. The reaction is extracted with EtOAc. The combined organic layer is washed with 1N HCl, H2O, sat. aq. NaHCO3 and brine and dried over anhydrous sodium sulfate, filtered and concentrated to give the crude residue. Next, to a solution of the obtained residue (0.252 g, 0.625 mmol) in DMSO (1.5 ml) at room temperature is added ammonium hydroxide (0.027 ml, 0.688 mmol). The reaction is stirred at room temperature. 30 min LCMS showed small desired product with big starting material so more ammonium hydroxide is added and the reaction is stirred at room temperature overnight until the reaction is complete. The reaction is extracted with EtOAc. The combined organic layer is washed with H2O, 1N HCl, H2O, 1 N NaOH and brine and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by column chromatography (2% to 6% EtOH/DCM) to give (R)-4-biphenyl-4-yl-3-ureido-butyric acid ethyl ester (169 mg). HPLC retention time=1.04 minutes (condition B); MS (m+1)=327.
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