5-benzylmorpholin-3-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (±)-5-(Phenylmethyl)-3-morpholinone, (U.S. Pat. No. 3,265,688) 5 g 0.026 mol), is suspended in a solution of 50 ml of concentrated hydrochloric acid and 50 ml of water and refluxed for six hours, cooled to room temperature and extracted with 200 ml of dichloromethane. The aqueous layer is separated, evaporated in vacuo, the residue dissolved in 200 ml of water, and the pH adjusted with a 10% aqueous solution of sodium hydroxide to pH 10-10.5. The solution is cooled to 5° C. and 5.1 g (0.03 mol) of benzylchloroformate is added dropwise while the pH is maintained at pH 10 with a 10% aqueous solution of sodium hydroxide. The mixture is stirred one hour, extracted with 100 ml of diethylether, the aqueous layer is separated and the pH is adjusted to pH 3-4 by the addition of a 10% aqueous solution of hydrochloric acid. The mixture is extracted with dichloromethane, 3×200 ml. The dichloromethane layer is separated, washed with a saturated aqueous solution of sodium chloride, 3×200 ml, separated, dried over sodium sulfate, evaporated and the residue is purified by chromatography using silica gel and eluting with dichloromethane-methanol (95:5) to give (±)-[3-phenyl[-2-[[(phenylmethoxy]carbonyl]amino]propoxy]acetic acid, 4 g; mp 96°-100°. refluxed for six hours extracted with 200 ml of dichloromethane The aqueous layer is separated evaporated in vacuo the residue dissolved in 200 ml of water The solution is cooled to 5° C. extracted with 100 ml of diethylether the aqueous layer is separated the pH is adjusted to pH 3-4 by the addition of a 10% aqueous solution of hydrochloric acid The mixture is extracted with dichloromethane, 3×200 ml The dichloromethane layer is separated washed with a saturated aqueous solution of sodium chloride, 3×200 ml separated dried over sodium sulfate evaporated the residue is purified by chromatography eluting with dichloromethane-methanol (95:5)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 60% NaH (80 mg, 2 mmol) in dry dimethylformamide (8 ml) was added 5-benzyl-3-morpholinone (880 mg, 2 mmol). The mixture was stirred at room temperature for 1 hour. To this were added 4-(3-chloro-3-phenylpropyl)morpholine (480 mg, 2 mmol) and dry dimethylforamide (1 ml). The mixture was then stirred overnight at 60° C. The stirred mixture was placed under reduced pressure to evaporate the solvent. Water was added to the residue, and extraction with ethyl acetate was performed. The extract was washed with a saturated aqueous brine and dried over anhydrous sodium sulfate. The dried extract was placed under reduced pressure to remove the solvent. The oily residue was placed on silica gel column and eluated with ethyl acetate/methanol (20/1) to yield the desired diastereomer A (168 mg, 21.3) and diastereomer B (156 mg, 19.8%). The mixture was then stirred overnight at 60° C to evaporate the solvent Water was added to the residue, and extraction with ethyl acetate The extract was washed with a saturated aqueous brine dried over anhydrous sodium sulfate The dried extract to remove the solvent to yield the desired diastereomer A (168 mg, 21.3) and diastereomer B (156 mg, 19.8%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 60% NaH (80 mg, 2 mmol) in dry dimethylformamide (8 ml) was added 5-benzyl-3-morpholinone (880 mg, 2 mmol). The mixture was stirred at room temperature for 1 hour. To this were added 4-(3-chloro-3-phenylpropyl)morpholine (480 mg, 2 mmol) and dry dimethylforamide (1 ml). The mixture was then stirred overnight at 60° C. The stirred mixture was placed under reduced pressure to evaporate the solvent. Water was added to the residue, and extraction with ethyl acetate was performed. The extract was washed with a saturated aqueous brine and dried over anhydrous sodium sulfate. The dried extract was placed under reduced pressure to remove the solvent. The oily residue was placed on silica gel column and eluated with ethyl acetate/methanol (20/1) to yield the desired diastereomer A (168 mg, 21.3%) and diastereomer B (156 mg, 19.8%). The mixture was then stirred overnight at 60° C to evaporate the solvent Water was added to the residue, and extraction with ethyl acetate The extract was washed with a saturated aqueous brine dried over anhydrous sodium sulfate The dried extract to remove the solvent to yield the desired diastereomer A (168 mg, 21.3%) and diastereomer B (156 mg, 19.8%)

Conditions: temp:0.00; pressure:0.00; stir: