Réaction #7411

Équation de réaction

6-chloro-N-{(3S)-1-[(1S)-1-methyl-2-oxo-2-piperidin-1-ylethyl]-2-oxopyrrolidin-3-yl}naphthalene-2-sulfonamide

lithium bis(trimethylsilyl) amide

lithium bis(trimethylsilyl) amide

bromoacetonitrile

→

title compound

Rendement 43.0%

6-Chloro-N-(cyanomethyl)-N-{(3S)-1-[(1S)-1-methyl-2-oxo-2-piperidin-1-ylethyl]-2-oxopyrrolidin-3-yl}naphthalene-2-sulfonamide

Rendement 43.0%

Solvants

THF

Conditions de réaction

Traitement

1. 1
   Autreto reach room temperature
2. 2
   AutreAfter reaching room temperature
3. 3
   workup.STIRRINGthe reaction mixture was stirred for a further 18 h
4. 4
   Autrequenched by the addition of methanol (1 ml)
5. 5
   ConcentrationThe resultant solution was concentrated under reduced pressure
6. 6
   Autrethe residue partitioned between water and DCM
7. 7
   AutreThe organic layer was separated
8. 8
   Séchagedried (over magnesium sulphate)
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    AutreThe residue was purified by mass

Mode opératoire

A solution of 6-chloro-N-{(3S)-1-[(1S)-1-methyl-2-oxo-2-piperidin-1-ylethyl]-2-oxopyrrolidin-3-yl}naphthalene-2-sulfonamide (0.015 g) in THF (2 ml) was cooled to −78° C. under nitrogen, and treated with lithium bis(trimethylsilyl) amide (1.0M solution in THF; 0.042 ml), followed by bromoacetonitrile (0.019 g). The resultant solution was allowed to reach room temperature and stirred for a further 16 h. The mixture was then cooled to −78° C. and further lithium bis(trimethylsilyl) amide (0.042 ml) added. After reaching room temperature, the reaction mixture was stirred for a further 18 h and then quenched by the addition of methanol (1 ml). The resultant solution was concentrated under reduced pressure and the residue partitioned between water and DCM. The organic layer was separated, dried (over magnesium sulphate) and concentrated under reduced pressure. The residue was purified by mass directed preparative h.p.l.c to give the title compound (0.007 g) as a colourless gum.

Source