[NH2:1][C@H:2]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[C:6]([F:13])[CH:5]=1)[CH3:3].[CH2:14](Cl)Cl.CCN([CH:23]([CH3:25])[CH3:24])C(C)C.[OH-:26].[Na+].CN1[C:33](=[O:34])CCC1>O>[C:23]([O:26][C:33]([NH:1][C@H:2]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[C:6]([F:13])[CH:5]=1)[CH3:3])=[O:34])([CH3:25])([CH3:14])[CH3:24]To (S)-4-(1-aminoethyl)-2-fluorobenzoic acid (900 mg, 4.10 mmol) was added, DCM (11 ml), Hunig's Base (2.147 ml, 12.29 mmol) and BOC-Anhydride (1.998 ml, 8.61 mmol). Then NMP (11.00 ml) was added to help solubility. The reaction was sonicated for 10 minutes and was stirred at room temperature for 22 hours, followed by LCMS. The DCM was mostly concentrated off. Then to the crude reaction was added 120 ml of water and basified with 10 ml of 5M NaOH. The basic aqueous solution was extracted with 2×50 ml of (15% ethyl acetate in heptane) solution. Then to the basic aqueous solution (with the product) was added 150 ml of ethyl acetate and with stirring acidified with 2M aqueous HCl solution to about pH 3. Then the ethyl acetate was extracted, saved and the acidic water extracted again with 100 ml of ethyl acetate. The organic layers were combined and washed with 0.5M aqueous HCl solution 1×40 ml, with water 3×40 ml, and concentrated to constant mass to give 1104 mg of (S)-4-(1-(tert-butoxycarbonylamino)ethyl)-2-fluorobenzoic acid, used as is. LCMS m/z BOC pattern of 269.0 (M+H-15 fragment) and weak 228.0 (M+H-56 fragment) compared to expected 284.0 (M+H)+, Rt 0.72 min.
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