Reaction #58533

Reaction equation

dithiocarbonic acid O-ethyl ester S-(3,3,3-trifluoro-2-oxo-propyl) ester

acetic acid

5-Oxo-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid ethyl ester

Lithium bis(trimethylsilyl)amide

→

subtitle product

Yield 24.5%

4-(1-Ethoxythiocarbonylsulfanylmethyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-oxo-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid ethyl ester

Yield 24.5%

Solvents

THF

toluene

THF

H2O

THF

THF

Conditions

Workup

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

Procedure

A 1M solution of Lithium bis(trimethylsilyl)amide in THF (LHMDS) (6.10 ml, 6.10 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 (1 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-(3,3,3-trifluoro-2-oxo-propyl) ester (1.3 g, 5.59 mmol) in THF (1 ml) was added dropwise over 25-30 minutes. After 3 hours at −700C, 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 a oily brown residue that was purified by silica-gel chromatography using a gradient of ethyl acetate/hexanes (0% to 100% ethyl acetate) to give the subtitle product as an oil (533 mg, 24%).

Source