9-Benzyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

To a stirred solution of 3-oxa-9-azabicyclo[3.3.1]nonan-7-one hydrochloride (1.26 g, 7.08 mmol, cas: 1126795-00-3, purchased from PharmaBlock (Nanjing) R&D Co. Ltd, ) and potassium carbonate (2.94 g, 14.16 mmol) in DMF (10 mL) was added benzyl bromide (1.33 g, 7.78 mmol) dropwise at room temperature. The resulting mixture was stirred at room temperature overnight, then concentrated and the residue was partitioned between HTo a solution of Mg (1.12 g, 46.1 mmol) and LiCl (1.95 g, 46.07 mmol) in THF (60 mL) at room temperature, 1 M DIBAL-H in toluene (0.58 mL) was added and stirred at room (1297) temperature for 30 min. l-Bromo-4-(methoxymethoxy)benzene (5.0 g, 23.0 mmol) was added dropwise at room temperature and then stirred at room temperature for 2 h. A solution of 9-benzyl- 3-oxa-9-azabicyclo[3.3. l]nonan-7-one (1.3 g, 5.62 mmol) in THF (60 mL) was added dropwise at room temperature and then stirred at room temperature overnight. The mixture was poured into aqueous sat. NH4Cl (200 mL) and filtered through celite pad. The filtrate was extracted with EtOAc (2 x300 mL). The organic layers were combined, washed with water (2 x l00 mL), brine (100 mL), dried (Na2S04), filtered, concentrated, and then purified by chromatography on silica gel (petoleum ether/EtOAc = 5/1) to give 9-benzyl-7-(4-(methoxymethoxy)phenyl)-3-oxa-9- azabicyclo[3.3. l]nonan-7-ol (1.2 g, 28%) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) d 7.61- 747 (m, 2H), 7.44-7.13 (m, 5H), 7.00-6.91 (m, 2H), 5.12 (s, 2H), 3.81-3.70 (m, 2H), 4.03-3.69 (m, 4H), 3.32 (s, 3H), 3.28 (s, 2H), 2.79-2.71 (m, 2H), 1.61-1.51 (m, 2H). LCMS: 370.2 [M+H]+.. To a solution of 1, 4-anhydroerythritol (4.9 g, 1 eq., 48 mmol), acetone-1, 3-dicarboxylic acid (7 g, 1 eq., 48 mmol) and HCl conc. (2.5 mL) in water (70 mL) was added benzylamine (6.14 mL, 1.38 eq., 66 mmol). The resulting reaction was allowed to stir for 1.5 h, then the reaction was heated to 50C. and allowed to stir at this temperature for 5 h. The reaction mixture was cooled to 0C., basified to pH 10 with 1N NaOH, and extracted with Et2O. The organic extract was dried over K2CO3, filtered and concentrated in vacuo, and the residue obtained was purified by flash chromatography eluting with cyclohexane/EtOAc (0 to 80%) to give the pure title compound as white solid (2.16 g, 19%). UPLC-MS (method A): Rt. 0.59 min (TIC); ionization ES+232 [M+H]+. 1H NMR (400 MHz, DMSO-d6): delta 7.47-7.39 (m, 2H), 7.39-7.32 (m, 2H), 7.30-7.21 (m, 1H), 3.90 (s, 2H), 3.68-3.53 (m, 4H), 3.06 (d, J=5.8 Hz, 2H), 2.77 (dd, J=15.8, 5.9 Hz, 2H), 2.18-2.04 (m, 2H).

Molecular Weight:231.29
XLogP3:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:231.125928785
Monoisotopic Mass:231.125928785
Topological Polar Surface Area:29.5
Heavy Atom Count:17
Complexity:270
Undefined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes