Sodium borohydride → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((3S)-5-hydroxyhexan-3-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

HRID 932089Notes

Reaction equation

HRID 932089 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]([CH2:24][C:25](=[O:27])[CH3:26])[CH2:22][CH3:23])[C:11](=[O:28])[C@:10]([CH2:30][C:31]([OH:33])=[O:32])([CH3:29])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+]>CCOCC.CO>[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]([CH2:24][CH:25]([OH:27])[CH3:26])[CH2:22][CH3:23])[C:11](=[O:28])[C@:10]([CH2:30][C:31]([OH:33])=[O:32])([CH3:29])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 67998885HCID 67998885, compound

Product 1

HCID 679993752-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((3S)-5-hydroxyhexan-3-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-5-oxohexan-3-yl)piperidin-3-yl)acetic acid (24 mg, 0.049 mmol; Example 130) in ether (0.40 mL) and MeOH (0.10 mL) was added sodium borohydride (9.26 mg, 0.245 mmol) at 0° C. Then the reaction was allowed to warm to rt. After being stirred at rt for 1 h, the reaction was quenched (10% citric acid) and extracted (2×EtOAc). The combined organic layer was washed (sat. aq. NaCl solution), dried (Na2SO4), and concentrated under reduced pressure. Purification by RP-HPLC (30 to 70% MeCN/H2O (0.1% TFA), a gradient elution) provided the title compound as the more polar isomer.

Workup

  1. customthe reaction was quenched (10% citric acid)
  2. extractionextracted (2×EtOAc)
  3. washThe combined organic layer was washed (sat. aq. NaCl solution)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customPurification by RP-HPLC (30 to 70% MeCN/H2O (0.1% TFA)
  7. washa gradient elution)

Sources & evidence

ORD record
ord-0436046ff85b45ab9936b6f6f26a4f3a
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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