Citric Acid → HCID 56591459, compound

HRID 931895Notes

Reaction equation

HRID 931895 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]([CH2:30][CH3:31])[CH2:22][O:23][CH2:24][C:25]3([C:28]#[N:29])[CH2:27][CH2:26]3)[C:11](=[O:32])[C@@H:10]([CH2:33][C:34]([OH:36])=[O:35])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[OH-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:42]>CC(O)(C)C>[C:28]([C:25]1([CH2:24][O:23][CH2:22][C@@H:21]([N:12]2[C@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[C@@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[CH2:9][C@H:10]([CH2:33][C:34]([OH:36])=[O:35])[C:11]2=[O:32])[CH2:30][CH3:31])[CH2:27][CH2:26]1)(=[O:42])[NH2:29]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14797Potassium HydroxideHCID 56591259HCID 56591259, compound

Product 1

HCID 56591459HCID 56591459, compound

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

A solution of 10 mg (0.02 mmol) 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-((1-cyanocyclopropyl)methoxy)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid (Example 11) and potassium hydroxide (3.2 mg, 0.06 mmol) in t-BuOH (189 μL) was stirred at 85° C. for 24 h. The reaction was acidified (10% citric acid) and extracted (2×EtOAc). The combined organic layers were washed with sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification by reversed phase preparatory HPLC (Gemini™ Prep C18 5 μm column, Phenomenex, Torrance, Calif.; eluent: 35 to 75% acetonitrile +0.1% TFA in water +0.1% TFA, gradient elution) provided the title compound.

Workup

  1. extractionextracted (2×EtOAc)
  2. washThe combined organic layers were washed with sat. NaCl solution
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customPurification
  7. washby reversed phase preparatory HPLC (Gemini™ Prep C18 5 μm column, Phenomenex, Torrance, Calif.; eluent: 35 to 75% acetonitrile +0.1% TFA in water +0.1% TFA, gradient elution)

Sources & evidence

ORD record
ord-cbad5d7dfcde43e6973d6a18a23ba7d0
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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