Réaction #3477

Équation de réaction

N-methoxy-N-methylpropanamide

sec-butyl lithium cyclohexane

N-tert-butoxycarbonyl-4-methoxy-2-methylaniline

→

1-(2-(tert-butoxycarbonylamino)-5-methoxyphenyl]-2-butanone

Rendement 74.3%

Solvants

THF

THF

Conditions de réaction

Traitement

1. 1
   Autrethe temperature below -40° C.
2. 2
   AutreThe bath was removed
3. 3
   Autreto rise to -20° C.
4. 4
   Autrethe cooling bath removed
5. 5
   workup.STIRRINGstirred an additional 1 hour
6. 6
   workup.ADDITIONIt was then poured into a mixture of 200 mL of ether and 200 mL of 1N HCl
7. 7
   AutreThe organic layer was separated
8. 8
   Lavagewashed with water
9. 9
   Autredried over Na2 SO4
10. 10
    Concentrationconcentrated at reduced pressure

Mode opératoire

A solution of 1.3M sec-butyl lithium/cyclohexane (81 mL, 0.105 mol) was added slowly to 11.85 g (0.05 mol) of N-tert-butoxycarbonyl-4-methoxy-2-methylaniline in 80 mL of THF while keeping the temperature below -40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to -20° C. and then the bath was replaced. After the temperature had cooled to -60° C., 6.1 g (0.052 mol) of N-methoxy-N-methylpropanamide in an equal volume of THF was added dropwise. The reaction mixture was stirred 1 hour, the cooling bath removed and stirred an additional 1 hour. It was then poured into a mixture of 200 mL of ether and 200 mL of 1N HCl. The organic layer was separated, washed with water, dried over Na2 SO4 and concentrated at reduced pressure to give 10.9 g (74% yield) of 1-(2-(tert-butoxycarbonylamino)-5-methoxyphenyl]-2-butanone, melting at 80°-81° C., after chromatography on silica eluting with 5% EtOAc/toluene.

Source