Triethylamine → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)-N'-hydroxyacetimidamide

HRID 931985Notes

Reaction equation

HRID 931985 reaction equation
Cl.[NH2:2][OH:3].C(N(CC)CC)C.[Cl:11][C:12]1[CH:13]=[C:14]([C@@H:18]2[C@@H:23]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[N:22]([CH:31]([CH2:34][CH3:35])[CH2:32][CH3:33])[C:21](=[O:36])[C@:20]([CH2:38][C:39]#[N:40])([CH3:37])[CH2:19]2)[CH:15]=[CH:16][CH:17]=1>CS(C)=O>[Cl:11][C:12]1[CH:13]=[C:14]([C@@H:18]2[C@@H:23]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[N:22]([CH:31]([CH2:34][CH3:35])[CH2:32][CH3:33])[C:21](=[O:36])[C@:20]([CH2:38][C:39](=[N:2][OH:3])[NH2:40])([CH3:37])[CH2:19]2)[CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 585731192-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetonitrile

Product 1

HCID 866607192-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)-N'-hydroxyacetimidamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
75 °C

Procedure

To a suspension of 1.49 g (20.6 mmol) of hydroxylamine hydrochloride in DMSO (10 mL) was added 2.88 mL (20.6 mmol) of triethylamine. The slurry was stirred for 5 min and then filtered twice through cotton, rinsing with THF, to remove the solids. The filtrate was partially concentrated under reduced pressure to remove THF, and then was added to a flask containing 915 mg (2.06 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetonitrile (Example 82, Step B). The resulting yellow solution was heated at 75° C. for 22 h, and then was partitioned between water and EtOAc. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (1 to 7% MeOH/DCM, gradient elution) provided the title compound as a white solid.

Workup

  1. filtrationfiltered twice through cotton
  2. washrinsing with THF
  3. customto remove the solids
  4. concentrationThe filtrate was partially concentrated under reduced pressure
  5. customto remove THF
  6. additionwas added to a flask
  7. customwas partitioned between water and EtOAc
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customPurification of the residue by flash chromatography on silica gel (1 to 7% MeOH/DCM, gradient elution)

Sources & evidence

ORD record
ord-2e427a5e33b649378606e132ee0824d9
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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