Hydrochloric Acid → 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)propanoic acid

HRID 1048383Notes

Reaction equation

HRID 1048383 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]([CH2:31][CH3:32])[CH2:22][N:23]([CH3:30])[S:24]([CH:27]3[CH2:29][CH2:28]3)(=[O:26])=[O:25])[C:11](=[O:33])[C@H:10]([CH:34]([CH3:39])[C:35]([O:37]C)=[O:36])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[Li+].[OH-].Cl>CO.C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([C@@H:21]([CH2:31][CH3:32])[CH2:22][N:23]([CH3:30])[S:24]([CH:27]3[CH2:28][CH2:29]3)(=[O:25])=[O:26])[C:11](=[O:33])[C@H:10]([CH:34]([CH3:39])[C:35]([OH:37])=[O:36])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 68000356Methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)propanoate

Product 1

HCID 680007172-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)propanoic acid

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)propanoate (56 mg, 0.094 mmol; Example 127, Step F) in MeOH/THF/H2O (1 mL/1 mL/2 mL) was added LiOH (3 M in water) (157 μL, 0.470 mmol) at room temperature. The slurry was heated to ˜100° C. for 3 h. The mixture was cooled to room temperature, acidified with 1 M HCl and extracted with EtOAc (2×). The organic layers were combined, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The colorless film was purified by reverse phase preparatory HPLC (column: Gemini-NX C18 5 um column; Phenomonex, Torrance, Calif.; eluent: 0 to 100% MeCN+0.1% TFA in water+0.1% TFA, over 20 minutes) to give the title compound.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with EtOAc (2×)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe colorless film was purified by reverse phase preparatory HPLC (column: Gemini-NX C18 5 um column; Phenomonex, Torrance, Calif.; eluent: 0 to 100% MeCN+0.1% TFA in water+0.1% TFA, over 20 minutes)

Sources & evidence

ORD record
ord-8d88bd284033411185ac1542f99f7ba9
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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