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 1048426Notes

Reaction equation

HRID 1048426 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-7203d4b77dcd4b5cade3d3d7d9e61736
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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