Hydrochloric Acid → (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-(3-methylpyridin-2-yl)piperidin-2-one

HRID 932026Notes

Reaction equation

HRID 932026 reaction equation
[CH2:1]([C@@:4]1([CH3:33])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C:24]2[C:29]([CH3:30])=[CH:28][C:27](N)=[CH:26][N:25]=2)[C:5]1=[O:32])[CH:2]=[CH2:3].Cl.OO.N([O-])=O.[Na+]>O1CCOCC1.C(O)(=O)C>[CH2:1]([C@@:4]1([CH3:33])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C:24]2[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][N:25]=2)[C:5]1=[O:32])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 23668193Sodium NitriteHCID 67998447(3S,5R,6S)-3-allyl-1-(5-amino-3-methylpyridin-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one

Product 1

HCID 67999123(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-(3-methylpyridin-2-yl)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (3S,5R,6S)-3-allyl-1-(5-amino-3-methylpyridin-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one (Example 113, Step B) (89 mg, 0.185 mmol) in 1,4-dioxane (4.0 mL) and acetic acid (0.50 mL) was added 3.0M HCl (730 μL, 2.2 mmol) at 0° C. After the reaction was stirred for 5 minutes, hydrogen peroxide (6% wt aq., 95 μL, 0.185 mmol) was added dropwise, followed by sodium nitrite (46 mg, 0.74 mmol). The reaction mixture was stirred for 2 hours at 0° C. The reaction mixture was warmed to room temperature, quenched with 1M NaOH 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 (0 to 55% EtOAc/Hex, gradient elution) provided the title compound as a colorless solid.

Workup

  1. stirringThe reaction mixture was stirred for 2 hours at 0° C
  2. customquenched with 1M NaOH
  3. extractionextracted (2×EtOAc)
  4. washThe combined organic layers were washed with sat. aq. NaCl solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customPurification of the residue
  9. washby flash chromatography (0 to 55% EtOAc/Hex, gradient elution)

Sources & evidence

ORD record
ord-d502d6a458574f0e99e7eec7b92422ae
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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