[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][C:3]=1[F:10].N1C=CC=CC=1.Cl[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19]>C1COCC1.[OH-].[Na+]>[CH2:21]([O:20][C:18](=[O:19])[NH:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][C:3]=1[F:10])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1To a mixture of 4-amino-3-fluorobenzylalcohol (20.7 g, 147 mmol) and pyridine (35.5 ml, 79 mmol) in THF (320 ml) and 2N NaOH (80 mL) was added benzyl chloroformate (24.8 mL, 170.6 mmol) at 0° C. over a period of 15 min. The reaction mixture was stirred for 20 min at 0° C. and for 2 h at room temperature. The reaction was quenched with water and diluted with EtOAc. The phases were separated and the organic phase was washed with 5% NaHSO4, saturated aq. NaHCO3 and brine, dried over Na2SO4, filtered and evaporated. The title compound was crystallized from EtOAc and cyclohexane: TLC (cyclohexane-EtOAc 3:1) Rf=0.45; HPLC RtE=1.02 min; ESIMS [M+NH4]+=293; ESIMS [M−H]−=274; 1H NMR (360 MHz, CDCl3): δ 8.00 (t, 1H), 7.40-7.25 (m, 5H), 7.10-7.00 (m, 2H), 6.82 (s broad, 1H), 5.15 (s, 2H), 4.55 (d, 2H).
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