Reaction #56614

Reaction equation

HCl

KOtBu

tosyl chloride

(4S)-N-allyl-4-hydroxy-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanamide

→

(5R)-1-Allyl-5-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone

Solvents

water

THF

THF

Conditions

Workup

1. 1
   Otherwhich had been dried
2. 2
   Temperatureby heating, in THF (5 ml, anhydrous)
3. 3
   workup.STIRRINGThe mixture is stirred at 0° C. for 2 h and at room temperature for 16 h
4. 4
   Extractionextracted with ethyl acetate
5. 5
   DryingThe combined organic phases are dried (Na2SO4)
6. 6
   Concentrationconcentrated
7. 7
   OtherThe residue (0.85 g, content: 81%, HPLC, 100% method) is further purified by flash chromatography (mobile phase: ethyl acetate/petroleum ether (40/60), 1:1)

Procedure

Under argon, KOtBu (0.64 g, 5.7 mmol) is suspended, in a Schlenk tube which had been dried by heating, in THF (5 ml, anhydrous). At 0° C., a solution of (4S)-N-allyl-4-hydroxy-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanamide (XVI-1) (0.99 g, 2.6 mmol) in THF (8 ml, anhydrous) is added dropwise. The reaction mixture is stirred at 0° C. for 1 h and a solution of tosyl chloride (0.52 g, 2.7 mmol) in THF (5 ml, anhydrous) is then added dropwise over a period of 20 min. The mixture is stirred at 0° C. for 2 h and at room temperature for 16 h. For work-up, the mixture is admixed with water, adjusted to pH 5 using HCl and extracted with ethyl acetate. The combined organic phases are dried (Na2SO4) and concentrated. The residue (0.85 g, content: 81%, HPLC, 100% method) is further purified by flash chromatography (mobile phase: ethyl acetate/petroleum ether (40/60), 1:1).

Source