[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:6][C:7]1[CH:14]=[C:13]([F:15])[C:10]([CH:11]=O)=[C:9]([Cl:16])[CH:8]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.O>[Cl:16][C:9]1[CH:8]=[C:7]([OH:6])[CH:14]=[C:13]([F:15])[C:10]=1[CH2:11][N:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1
Pyrrolidine (4.65 mL, 56 mmol) was added to a solution of intermediate 17, 4-hydroxy-2-chloro-6-fluorobenzaldehyde (7.5 g, 43 mmol) in dichloromethane (100 mL). The reaction mixture was cooled on ice bath, and sodium triacetoxyborohydride (13.71 g, 65 mmol) was added in portions under stirring. The reaction mixture was intensively stirred for 24 h at RT. Water (100 mL) and concentrated HCl were added to attain pH˜2. The organic layer was separated. The aqueous one was extracted with CH2Cl2 (2×100 mL), then with EtOAc (100 mL). The organic layers were discarded. The aqueous fraction was alkalized with K2CO3 to pH˜10, the obtained crystals were separated by filtration, dried in vacuo, recrystallized from Et2O/hexane mixture (1:1) to give the title compound (7 g, 71%, 30 mmol). LCMS data: 231 and 230 (M+H)+ (calculated for C11H13ClFNO 229.7). 1H NMR data (DMSO-d6): 10.25 (br.s, 1H, OH), 6.66-6.70 (m, 1H, H—Ar), 6.54 (dd, 1H, J1=2.2 Hz, J2=11.3 Hz, H—Ar), 3.58 (d, 2H, J1=2.4 Hz, Ar—CH2); 2.38-2.46 (m, 4H), 1.58-1.68 (m, 4H).
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