Process for preparing Ezetimibe intermediate by enantioselective CBS catalyzed ketone reduction with BH3-DEA prepared in situ

Tetrahedron Letters

Volumn 48, Issue 12, 2007, Pages 2123-2125

  Bertrand, Blandine ^a   Durassier, Sonia ^a   Frein, Stéphane ^a   Burgos, Alain ^a  

^a PPG SIPSY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

EZETIMIBE;

ARTICLE; CATALYSIS; CHEMICAL REACTION; COST BENEFIT ANALYSIS; DRUG SYNTHESIS; ENANTIOSELECTIVITY; INDUSTRIALIZATION; REDUCTION; SOLVATION; SYNTHESIS; TEMPERATURE MEASUREMENT;

EID: 33847032925     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2007.01.118     Document Type: Article

References (10)

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10. 4 was added slowly to the previous suspension. The reaction was maintained at 40 °C until a clear solution was obtained. 286 mg (6.8 mmol) of LiCl was then added. The reaction mixture was then cooled to room temperature (20 °C) then 1.7 ml of a 1 M (R)-MeCBS in toluene (1.7 mmol) was added. Ketone 1 [12 g (33.8 mmol)] was dissolved in 24 ml of THF and added over a 1 h period to the previous reaction mixture. The reaction was then maintained at 20 °C for 10 min then 6 g (100 mmol) of acetone was rapidly added. 6.07 g (43.9 mmol) of potassium carbonate was dissolved in 72 ml of water. The reaction mixture was then added to the carbonate solution. The aqueous phase was discarded. The organic phase was partially concentrated and taken up in 72 ml of toluene. The organic phase was washed with 36 ml of water, twice with 30 ml of 10% sulfuric acid (50 mmol) then with 36 ml of water. The organic phase was concentrated under vacuum to dryness to give 13 g of a viscous oil, compound 2.