Sodium Hydroxide → HCID 67055313, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6.90 g (13.07 mmol) of 3-[(S)-{3-[(1S)-1-(3-bromo-5-fluorophenyl)-2-hydroxy-2-methylpropyl]azetidin-1-yl}(4 chlorophenyl)methyl]benzonitrile, 50 mL of hydrogen fluoride pyridine (HF 70%), and 60 mL of 1,2-dichloroethane was stirred at 40-42° C. for 16 h. Then the reaction mixture was poured slowly to a mixture of 250 mL of water, 74 g of NaOH, 300 mL of aq NaHCO3, 300 g of ice and 500 mL of CH2Cl2 with rapid stirring. The pH of the mixture was adjusted to 7-8, and the mixture was filtered to remove solids. The aqueous layer was extracted with three 300 mL portions of CH2Cl2. The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexane/ethyl acetate to afford the title compound as a white solid; 1H-NMR(CDCl3) δ 1.25 (t, 6H, J=11.8 Hz), 2.32(t, 1H, J=7.5 Hz), 2.83-2.89(m, 2H), 3.09-3.17(m, 2H), 3.59 (m, 1H), 4.26(s, 1H), 6.85 (d, 1H, J=9.1 Hz), 7.10-7.14(m, 2H), 7.28-7.33 (m, 4H), 7.36 (t, 1H, J=7.2 Hz), 7.46 (d, 1H, J=7.8 Hz), 7.56 (d, 1H, J=7.7 Hz), 7.67 (s, 1H); Mass Spectrum: m/e=529, (M+1, 35Cl 79Br), 531 (M+1, 37Cl79Br/35Cl 81Br), 533 (M+1, 37Cl81Br).

Provenance & Evidence