[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:6][C:7]1[C:14]([OH:15])=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.O>[Cl:6][C:7]1[C:8]([CH2:9][N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:11][CH:12]=[CH:13][C:14]=1[OH:15]
Pyrrolidine (71.3 mL, 855 mmol) was added to a solution of intermediate 12, 2-chloro-3-hydroxybenzaldehyde (103 g, 658 mmol) in dichloromethane (1 L). The reaction mixture was cooled on ice bath, and sodium triacetoxyborohydride (209.3 g, 987 mmol) was added in portions under stirring. The reaction mixture was stirred for 12 h at room temperature. Water (500 mL) and concentrated HCl were added to attain pH˜2. The organic layer was separated. The aqueous one was extracted with CH2Cl2 (2×400 mL), then with EtOAc (400 mL). The organic layers were discarded. The aqueous fraction was alkalized with K2CO3 to pH˜10, and the product was extracted with CHCl3 (3×500 mL). The organic layer was dried with Na2SO4 and evaporated in vacuo. The obtained crystals were separated by filtration from Et2O/hexane mixture (1:1) and coevaporated with dioxane to give the title compound (76 g, 55%, 359 mmol). LCMS data: 214 and 212 (M+H)+ (calculated for C11H14ClNO 211.7); 1H NMR data (DMSO-d6): 9.96 (br.s, 1H, OH); 7.08 (t, 1H, J=7.8 Hz, Ar—H); 6.91 (dd, 1H, J1=1.7 Hz, J2=7.3 Hz, Ar—H); 6.86 (dd, 1H, J1=1.7 Hz, J2=8.0 Hz, Ar—H); 3.64 (s, 2H, CH2Ar); 2.43-2.52 (m, 4H+DMSO); 1.65-1.74 (m, 4H).
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