Trifluoroacetic acid → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetonitrile

HRID 1048296Notes

Reaction equation

HRID 1048296 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@:10]([CH2:28][C:29]([NH2:31])=O)([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.C(O)(C(F)(F)F)=O>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@:10]([CH2:28][C:29]#[N:31])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 585737522-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetamide

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 1.15 g (2.49 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetamide (Example 82, Step A) in THF (21 mL) was added 1.73 mL (12.4 mmol) of triethylamine and 865 μL (6.22 mmol) of TFA. The resulting tan solution was stirred at 0° C. for 2.75 h, then was warmed to room temperature and stirred for an additional 2 h. The reaction was recooled to 0° C., quenched with 1 N citric acid, and then extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. The combined organic layers were washed with saturated aqueous sodium chloride (1×), then were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (5 to 35% EtOAc/hexanes, gradient elution) provided the title compound as a white solid.

Workup

  1. temperaturewas warmed to room temperature
  2. stirringstirred for an additional 2 h
  3. customwas recooled to 0° C.
  4. customquenched with 1 N citric acid
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. washThe combined organic layers were washed with saturated aqueous sodium chloride (1×)
  10. dry with materialwere dried over Na2SO4
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated
  13. customPurification of the residue by flash chromatography on silica gel (5 to 35% EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-d2d185b48cfd4dc39b2800fd3598d45e
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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