3-BENZYL-3-AZABICYCLO[3.2.1]OCTAN-8-ONE

Intermediate I-32 (3-benzyl-3-azabicyclo[3.2.1]octan-8-one)A 2-L round-bottom flask equipped with condenser and nitrogen inlet was charged with benzyl amine (127 g, 1.2 mol, 1.0 eq) and methanol (800 mL), and glacial acetic acid (127 g, 1.2 mol, 1.0 eq) was added drop wise. Intermediate I-31 (100 g, 1.2 mol, 1.0 eq) was added followed by paraformaldehyde (107 g, 3.6 mol, 3.0 eq) and the reaction mixture was stirred at 80° C. for 3 hours and then at room temperature for additional 18 hours. Excess solvent was removed by evaporation, the residue was diluted with ethyl acetate and solid sodium metabisulphite (104 g) was added. The crude reaction mixture was stirred for additional 1.5 hours and extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na0.26 g (1 mmol) of compound (1') purified on a silica gel column was dissolved in 1, 4-dioxane (1 ml), to which 30percent fuming sulfuric acid (0.3 ml) was added dropwise and stirred for 30 min. The reaction solution was poured into an ice-cold water, which was then neutralized with 1M aqueous sodium hydroxide and extracted with hexane/ethyl acetate. The organic layer was washed with a saturated saline, dried with magnesium sulfate, filtered and concentrated to obtain 3-Benzyl-3-aza-bicyclo[3.2.1]octan-8-one compound (3) as a crude purification product. A HPLC analysis revealed that the yield was 96.0percent.Preparation 323-benzyl-3-azabicyclo[3.2.noctan-8-one; Cyclopentanone (16.8g, 0.2mol) was dissolved in acetic acid (30OmL) and benzylamine (28.7g, 0.2mol) and formaldehyde (49mL, 0.6mol) were added. The mixture was heated to reflux for 5 hours and then allowed to cool to room temperature. The reaction mixture was concentrated in vacuo and diluted with water (15OmL). The aqueous solution was washed with ethyl acetate (2 x 10OmL) and then basified with solid potassium carbonate. The aqueous layer was extracted with ethyl acetate (3 x 15OmL). The combined organic extracts were dried over magnesium sulfate and then concentrated in vacuo. The residue was purified by column chromatography on silica gel using pentane:ethyl acetate 80:20 as eluent to give the title compound, 1.36g (3percent) as a white solid. LRMS: m/z APCI+216 [MHPreparation A

Molecular Weight:215.29
XLogP3:1.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:215.131014166
Monoisotopic Mass:215.131014166
Topological Polar Surface Area:20.3
Heavy Atom Count:16
Complexity:254
Undefined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes