N-Selectride® → {(3r,5r,6s)-5-(3-Chlorophenyl)-6-(4-Chlorophenyl)-1-[(2s,3s)-2-Hydroxypentan-3-Yl]-3-Methyl-2-Oxopiperidin-3-Yl}acetic Acid

To a solution of 3.86 g (8.13 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-2-oxopentan-3-yl)piperidin-3-yl)acetic acid (Example 151) in THF (102 mL) was added a 1 M solution of sodium tri-sec-butylborohydride (N-Selectride®, Aldrich, St. Louis, Mo.) in THF (16.26 mL, 16.26 mmol) at −78° C. dropwise over a period of 5 min. After being stirred at −78° C. for 30 min, the reaction was allowed to warm to rt. The reaction was stirred at rt for 2 h, the reaction was quenched (sat. NH4Cl solution), extracted (3×EtOAc) and washed (3×ice-cold 1 N aq. HCl and 3×saturated aqueous sodium chloride). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude material was purified by chromatography on a Biotage Isolera flash purification system (Biotage, Charlotte, N.C.) (2×1500 g columns, using a gradient from 10-30% (15% MeOH/acetone) in hexanes. The purified material was then recrystallized from 3:1 hexane/acetone (8 mL/g) to provide the title compound.

1. temperatureto warm to rt
2. stirringThe reaction was stirred at rt for 2 h
3. customthe reaction was quenched (sat. NH4Cl solution)
4. extractionextracted (3×EtOAc)
5. washwashed (3×ice-cold 1 N aq. HCl and 3×saturated aqueous sodium chloride)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe crude material was purified by chromatography on a Biotage Isolera flash purification system (Biotage, Charlotte, N.C.) (2×1500 g columns
10. customThe purified material was then recrystallized from 3:1 hexane/acetone (8 mL/g)

ORD 기록

ord-27733bcb13bd444cb3ee83ff49a65722

출처 데이터셋

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09296736B2