Réaction #10286

ord-17af3ceeed304966aae96f3eace54d08

Conditions de réaction

Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    Températurethe mixture was heated
  2. 2
    Températureto reflux
  3. 3
    Autrethe reaction
  4. 4
    workup.STIRRINGThe reaction mixture was stirred at room temperature for 16 hrs
  5. 5
    Autrecrushed ice
  6. 6
    ExtractionThe mixture was extracted with two 50 mL portions ethyl acetate
  7. 7
    LavageThe organic phase was washed with 25 mL saturated sodium chloride
  8. 8
    Séchagedried (magnesium sulfate)
  9. 9
    Concentrationconcentrated under reduced pressure

Mode opératoire

To a suspension of 0.85 g (34.6 mmole) magnesium turnings in 25 mL tetrahydrofuran was added 5 mL of a solution of 5 g (28.8 mmole) 1-bromo-4-tert-butylbenzene in 25 mL tetrahydrofuran. One iodine crystal and 1,2-dibromoethane (0.3 mL) was added and the mixture was heated to reflux to initiate the reaction. The rest of the 1-bromo-4-tert-butylbenzene solution was then added dropwise and the reaction mixture was stirred at room temperature for 1 hr. The remaining magnesium was allowed to settle and the supernatant was added in portions to a cooled, previously prepared mixture of 8 g (27.4 mmole) ((S)-1-methyl-2-morpholin-4-yl-2-oxoethyl)-carbamic acid benzyl ester n in 30 mL tetrahydrofuran and 30 mL (60 mmole) 2M isopropylmagnesium chloride in diethyl ether. The reaction mixture was stirred at room temperature for 16 hrs. The mixture was then added to a well-stirred mixture of 100 mL 5% hydrochloric acid and crushed ice. The mixture was extracted with two 50 mL portions ethyl acetate. The organic phase was washed with 25 mL saturated sodium chloride, dried (magnesium sulfate) and concentrated under reduced pressure. (S)-2-(4-tert-Butylphenyl)-1-methyl-2-oxoethyl]-carbamic acid benzyl ester o was isolated as a solid, 9.2 g. m.p. 156–158° C.

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US07094778B2uspto-grants-2006_08