Toluene → (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-2-hydroxy-2-methylpentan-3-yl)-3-methylpiperidin-2-one

HRID 932112Notes

Reaction equation

HRID 932112 reaction equation
[CH2:1]([C@@:4]1([CH3:31])[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@@H:24]([CH2:28][CH3:29])[C:25](=[O:27])[CH3:26])[C:5]1=[O:30])[CH:2]=[CH2:3].[CH3:32][Mg]Br.C1(C)C=CC=CC=1>C1COCC1>[CH2:1]([C@@:4]1([CH3:31])[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:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[N:6]([C@@H:24]([CH2:28][CH3:29])[C:25]([OH:27])([CH3:32])[CH3:26])[C:5]1=[O:30])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 1140TolueneHCID 58573535(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-2-oxopentan-3-yl)piperidin-2-oneHCID 178418573HCID 178418573, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 58573578(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-2-hydroxy-2-methylpentan-3-yl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-2-oxopentan-3-yl)piperidin-2-one (0.100 g, 0.218 mmol; Example 149, Step B) in THF (4 mL) was added a solution of methylmagnesium bromide, 1.4M in toluene (0.104 g, 0.873 mmol) at 0° C. The reaction was allowed to warm to room temperature. After being stirred at room temperature for 4 h, another 1 eq. of MeMgBr was added and stirred for another 2 h. The reaction was quenched w/sat NH4Cl solution, and extracted with EtOAc. The combined organic layers were washed with sat. aq. NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The crude material was absorbed onto a plug of silica gel and purified by chromatography on silica gel, eluting with 40% EtOAc/hexanes, to provide the title compound as a light-yellow oil.

Workup

  1. stirringstirred for another 2 h
  2. customThe reaction was quenched w/sat NH4Cl solution
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with sat. aq. NaCl solution
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe crude material was absorbed onto a plug of silica gel
  9. custompurified by chromatography on silica gel
  10. washeluting with 40% EtOAc/hexanes

Sources & evidence

ORD record
ord-824af59a25a14ec290da292c45913875
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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