(5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(2,4-dimethoxybenzyl)-3-methylpiperidin-2-one → (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one

HRID 931968Notes

Reaction equation

HRID 931968 reaction equation
[CH2:1]([C:4]1([CH3:36])[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](CC2C=CC(OC)=CC=2OC)[C:5]1=[O:35])[CH:2]=[CH2:3]>C(O)(C(F)(F)F)=O>[CH2:1]([C@@:4]1([CH3:36])[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)[NH:6][C:5]1=[O:35])[CH:2]=[CH2:3]

Participants

3

Reactant 1

HCID 58573739(5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(2,4-dimethoxybenzyl)-3-methylpiperidin-2-one

Product 1

HCID 58574008(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(2,4-dimethoxybenzyl)-3-methylpiperidin-2-one (Example 71, Step C, mixture of diastereomers) (105.87 g, 202 mmol) in TFA (778 mL, 1.01E+04 mmol) was heated at 50° C. for 2 hours before concentrating the reaction mixture in vacuo. The residue was azeotroped with hexanes to remove all of the TFA. The deep purple oil containing some residue was taken up in a minimum amount of DCM, filtered and washed liberally with DCM. The filtrate was concentrated in vacuo to provide a dark purple oil. Purification (wet packed with a minimum amount of DCM) using the Biotage Isolera (Biotage, Charlotte, N.C.) with a 1.5 kg column and eluting with 25-40% EtOAc/hexanes provided the title compound as a white solid.

Workup

  1. concentrationbefore concentrating the reaction mixture in vacuo
  2. customThe residue was azeotroped with hexanes
  3. customto remove all of the TFA
  4. additionThe deep purple oil containing some residue
  5. filtrationfiltered
  6. washwashed liberally with DCM
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto provide a dark purple oil
  9. customPurification (
  10. washeluting with 25-40% EtOAc/hexanes

Sources & evidence

ORD record
ord-946edf6f209642b19503e6001eb3f5c8
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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