Reaction #48746

Reaction equation

(2R,3S,5R)-5-[(1S,2S)-2-Acetylamino-1-hydroxy-3-(3-hydroxy-phenyl)-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid benzyl ester

cyclopropylmethyl bromide

cesium carbonate

N,N-dimethylformamide

→

desired compound

Yield 85.9%

N-{(S)-2-(3-Cyclopropylmethoxy-phenyl)-1-[(1S,5S,6R,8aR)-6-(2,2-dimethyl-propoxy)-5-methyl-3-oxo-tetrahydro-oxazolo[4,3-c][1,4]oxazin-1-yl]-ethyl}-acetamide

Yield 85.9%

Solvents

ethyl acetate

Conditions

Workup

1. 1
   TemperatureHeat
2. 2
   TemperatureCool
3. 3
   Washwash with saturated sodium chloride
4. 4
   Dryingdry with magnesium sulfate
5. 5
   Otherpurify on silica gel with dichloromethane/ethyl acetate

Procedure

Heat a mixture of (2R,3S,5R)-5-[(1S,2S)-2-Acetylamino-1-hydroxy-3-(3-hydroxy-phenyl)-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid benzyl ester (69 mg, 0.13 mmol), cyclopropylmethyl bromide (0.019 ml, 0.195 mmol), cesium carbonate (127 mg, 0.39 mmol) and N,N-dimethylformamide (2 mL) to 60° C. for 18 hours. Cool and dilute with ethyl acetate and wash with saturated sodium chloride, dry with magnesium sulfate and purify on silica gel with dichloromethane/ethyl acetate mixtures to give the desired compound (53 mg). MS(ESI): m/z=475 [M+H]+.

Source