2-methyl-1-morpholin-4-ylpropan-2-ol

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

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of N-(2-oxopropyl)morpholine (82 g, 0.57 mmol) in diethyl ether (400 ml) was added to a solution of 3M CH3MgBr (500 ml, 1.5 ml) in anhydrous diethyl ether (21) and stirred at 0° C. under an argon atmosphere. The mixture was stirred at ambient temperature for 16 hours, treated with 12N HCl (50 ml) and extracted with ethyl acetate. The product was purified by flash column chromatography eluting with ethyl acetate to give N-(2-hydroxy-2-methylpropyl)morpholine. The mixture was stirred at ambient temperature for 16 hours extracted with ethyl acetate The product was purified by flash column chromatography eluting with ethyl acetate

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

Procedure: A solution of N-(2-hydroxy-2-methylpropyl)morpholine (9.8 g, 62 mmol), N-benzyloxycarbonyl-L-methionine (12.6 g, 44 mmol), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (25 g, 54 mmol), DMAP (5.4 g, 44 mmole) in dichloromethane (250 ml) was stirred, in the presence of 4 Å molecular sieves (5 g), at ambient temperature for 48 h. After evaporation to dryness, the mixture was taken up in diethyl ether and the insoluble material eliminated by filtration. The organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated solution of brine, evaporated to dryness and purified by flash column chromatography eluting with dichloromethane/ethanol (98:2) to give 2-(morpholinomethyl)prop-2-yl (2S)-2-(benzyloxycarbonylamino)-4-methylsulfanylbutyrate (40%). After evaporation to dryness the insoluble material eliminated by filtration The organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate a saturated solution of brine, evaporated to dryness purified by flash column chromatography eluting with dichloromethane/ethanol (98:2)