3-benzyl-8-oxa-3-aza-bicyclo[3.2.1]octane synthesis

Yield:-

Reaction Conditions:

in toluene; for 18 h;Heating / reflux;

Steps:

To a mechanically stirred suspension of silica-supported NaIO₄ (240 g) in THF (1260 mL) and CH₂Cl₂ (138 mL) at 0° C. was added 1,5-hexadiene (8.5 mL) followed by addition in drops of a 0.01 M aqueous solution of RuCl₃ (14.4 mL). After 1.5 h, iPrOH (300 mL) was added. Stir 10 min, then filter, wash silica with EtOAc and concentrate filtrate. Pass oil through silica gel eluting with Et₂O, EtOAc and 5% MeOH/CHCl₃. Yields a clear oil (9.5 g). This material was dissolved in pyridine (90 mL) at 0° C. A solution of TsCl (31 g) in pyridine (36 mL) was added in drops. Allow to warm to RT. After 18 h H₂O (300 mL) was added. The white solid was collected by filtration and dried (12 g). This material in toluene (60 mL) was treated with benzylamine (10 mL). Heat at reflux for 18 h. Filter and concentrate in vacuo. Purify by vacuum distillation (5.7 g). This compound (7.3 g) in 1,2-dichloroethane (150 mL) was treated with 1-chloroethyl chloroformate (12 mL) and K₂CO₃ (15 g) and heated at reflux overnight. Filter using CH₂Cl₂. Concentrate, take up in EtOH and add 12 N HCl (5 mL). Concentrate. Add acetone and filter (4.5 g).

References:

US2009/98086,2009,A1 Location in patent:Page/Page column 63