Reaction #58531

ord-584d633cf4e34a31806a25434956f8ed

Conditions

Temperature
-30°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.STIRRINGthe reaction mixture was stirred for an additional 30 minutes
  2. 2
    Otherwas lowered to −70° C.
  3. 3
    workup.WAITAfter 3 hours at −70° C.
  4. 4
    Temperaturethe reaction mixture was warmed to 0° C
  5. 5
    Otherthe organic layer separated
  6. 6
    Dryingdried (MgSO4)
  7. 7
    Concentrationconcentrated
  8. 8
    Otherproviding oily brown residue that
  9. 9
    Otherwas purified by silica-gel chromatography

Procedure

A 1M solution of Lithium bis(trimethylsilyl)amide in THF (LHMDS) (6.08 ml, 6.08 mmol) was added to anhydrous THF (4 ml) and the mixture was cooled to −30° C. under N2. Next, a solution of 5-Oxo-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid ethyl ester (1.0 g, 5.07 mmol) in THF (10 ml) was added dropwise over 15 minutes and the mixture was stirred for an additional 15 minutes. Next, a 0.5M solution of ZnCl2 (15.2 ml, 7.6 mmol) was added over 15 minutes and the reaction mixture was stirred for an additional 30 minutes. The reaction temperature was lowered to −70° C. and a solution of dithiocarbonic acid O-ethyl ester S-(2-oxo-ethyl) ester (913 mg, 5.57 mmol) in THF (1 ml) was added dropwise over 25-30 minutes. After 3 hours at −70° C., a solution of acetic acid (2.5 ml) in toluene (7.5 ml) was added and the reaction mixture was warmed to 0° C. The reaction mixture was diluted with H2O (7.5 ml) and the organic layer separated, dried (MgSO4), and concentrated providing oily brown residue that was purified by silica-gel chromatography using a ethyl acetate/hexanes gradient (0% ethyl acetate to 100% ethyl acetate) to give the subtitle product as an oil (756 mg, 41%).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07423056B2uspto-grants-2008_09