Réaction #7314

Équation de réaction

HCl

cinchonine

pyridine

2-benzoylpyridine

tetrahydrofuran

tetrahydrofuran

→

tert-butyl 3-hydroxy-3-phenyl-3-(pyridin-2-yl)propionate

Rendement 98.0%

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONto this suspension was added a Reformatsky reagent (0.5 M; 8.0 mL, 4.0 mmol) dropwise under ice-
2. 2
   Températurecooling
3. 3
   workup.STIRRINGAfter stirring for 20 minutes under ice-
4. 4
   Températurecooling
5. 5
   workup.STIRRINGthe mixture was stirred at −40° C. for 4 hours
6. 6
   Extractionwas then extracted with ethyl acetate (20 mL×2)
7. 7
   LavageThe extracted solution was washed successively with an aqueous saturated sodium bicarbonate solution
8. 8
   SéchageAfter the organic layer was dried with sodium sulfate
9. 9
   Autrethe solvent was removed under reduced pressure

Mode opératoire

Under argon atmosphere, cinchonine (440 mg, 1.0 mmol) was suspended in tetrahydrofuran (absolute, 2.0 mL), and to this suspension was added a Reformatsky reagent (0.5 M; 8.0 mL, 4.0 mmol) dropwise under ice-cooling. After stirring for 10 minutes, pyridine (0.30 mL, 2 mmol) was added thereto dropwise. After stirring for 20 minutes under ice-cooling, the mixture was cooled to −40° C. A solution of 2-benzoylpyridine (183 mg, 1.0 mmol) in tetrahydrofuran (absolute, 4.0 mL) was added dropwise over 10 minutes, and the mixture was stirred at −40° C. for 4 hours. To this reaction solution was added 1N HCl (20 mL), which was then extracted with ethyl acetate (20 mL×2). The extracted solution was washed successively with an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution. After the organic layer was dried with sodium sulfate, the solvent was removed under reduced pressure. The residue was analyzed with high performance liquid chromatography. Consequently, the yield was 98% and the enantiomer excess was 90%.

Source