Reaction #7411

Reaction equation

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

Yield 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

Yield 43.0%

Solvents

THF

Conditions

Workup

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

Procedure

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