Hydrazine hydrate (1:1) → 2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetohydrazide

HRID 931928Notes

Reaction equation

HRID 931928 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]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:11](=[O:25])[C@@H:10]([CH2:26][C:27](OC)=[O:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.O.[NH2:32][NH2:33]>CCO>[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]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:11](=[O:25])[C@@H:10]([CH2:26][C:27]([NH:32][NH2:33])=[O:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 56591325Methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetate

Product 1

HCID 565912152-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetohydrazide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 120 mg (0.27 mmol) of methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetate (Example 47) in EtOH was added hydrazine, monohydrate (135 μl, 2688 μmol). After being refluxed for 14 h, the reaction was concentrated, diluted (H2O) and extracted (2×EtOAc). The combined organic layers were washed with sat. aq. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography on silica gel (5% MeOH/CH2Cl2, gradient elution) provided the title compound as a white solid.

Workup

  1. temperatureAfter being refluxed for 14 h
  2. concentrationthe reaction was concentrated
  3. additiondiluted (H2O)
  4. extractionextracted (2×EtOAc)
  5. washThe combined organic layers were washed with sat. aq. NaCl solution
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customPurification of the residue by flash chromatography on silica gel (5% MeOH/CH2Cl2, gradient elution)

Sources & evidence

ORD record
ord-ce11211b2f914bdab678fe702bc8bcb7
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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