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

HRID 932103Notes

Reaction equation

HRID 932103 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:25][CH3:26])[C:22](=[O:24])[CH3:23])[C:11](=[O:27])[C@:10]([CH2:29][C:30]([OH:32])=[O:31])([CH3:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C([BH-](C(CC)C)C(CC)C)(CC)C.[Na+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:25][CH3:26])[C@@H:22]([OH:24])[CH3:23])[C:11](=[O:27])[C@:10]([CH2:29][C:30]([OH:32])=[O:31])([CH3:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 5129077N-Selectride®HCID 585734892-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-2-oxopentan-3-yl)piperidin-3-yl)acetic acid

Product 1

HCID 56965957{(3r,5r,6s)-5-(3-Chlorophenyl)-6-(4-Chlorophenyl)-1-[(2s,3s)-2-Hydroxypentan-3-Yl]-3-Methyl-2-Oxopiperidin-3-Yl}acetic Acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-27733bcb13bd444cb3ee83ff49a65722
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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