Hydrochloric Acid → HCID 59166871, compound

Participants

Reaction Steps

(S)-2-[(S)-(2-Bromo-pyridin-3-yloxy)-phenyl-methyl]-morpholine was synthesized from the corresponding amide (6-[Phenyl-(pyridin-3-yloxy)-methyl]-morpholin-3-one) using the following procedure: To a solution of compound 1 (0.4 g, 1.1 mmol) in anhydrous tetrahydrofuran (10 mL) under a nitrogen atmosphere was added a commercial solution of borane-tetrahydrofuran complex (1.0M in tetrahydrofuran, 3.4 mL, 3.4 mmol) via syringe. The reaction mixture was stirred at room temperature for 20 h. TLC analysis showed no reaction had occurred. A further amount of borane-tetrahydrofuran complex (3.0 mL, 3.0 mmol) was added and the reaction mixture was heated at reflux for 2.5 h. TLC analysis showed no starting material. The reaction mixture was brought to room temperature, treated with 1N HCl, stirred for 30 minutes, basified by the addition of 2N sodium hydroxide and extracted with ethyl acetate. The combined organic extracts were dried over sodium sulphate, filtered, and solvent was removed under reduced pressure. Two chromatographies of the reaction product on silica gel (eluent—3:1 ethyl acetate/methanol for first chromatography, 10:1 dichloromethane/methanol for the second) gave 0.063 g (16%) of the desired product. 1H NMR (400 MHz, CDCl3) δ 7.90 (m, 1H), 7.36 (m, 5H), 7.00 (m, 2H), 5.16 (d, 1H), 3.96 (m, 2H), 3.68 (m, 1H), 2.82 (m, 2H), 2.64 (m, 2H), 1.80 (br s, 1H). (MS) m/z 350.92 [Cl6H17BrN2O2+H+] HPLC—91.49% CHN—C22H21FN2O2 Calc'd: C, 55.03%; H, 4.91%; N, 8.02%. Found: C, 55.01%; H, 4.97%; N, 8.60%.

Provenance & Evidence