Trifluoroacetic acid → HCID 68000991, compound

HRID 1048370Notes

Reaction equation

HRID 1048370 reaction equation
C(OC(=O)[C@@H]([N:10]1[C@H:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=2)[C@@H:14]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[CH2:13][C@@:12]([CH2:31][C:32](O)=O)([CH3:30])[C:11]1=[O:35])CC)(C)(C)C.[C:37](O)(C(F)(F)F)=O>>[CH2:31]([C@@:12]1([CH3:30])[CH2:13][C@H:14]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[C@@H:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=2)[NH:10][C:11]1=[O:35])[CH:32]=[CH2:37]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58573756HCID 58573756, compound

Product 1

HCID 68000991HCID 68000991, compound

Procedure

(5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-(2,4-dimethoxybenzyl)-3-methylpiperidin-2-one (3.6 g, 6.85 mmol, mixture of C-3 epimers, Example 124, Step B) was dissolved in TFA (26.4 mL, 343 mmol) and the reaction was heated to 70° for 1.5 h. It was then cooled to ambient temperature and the TFA was removed by concentration under reduced pressure. The product was azeotroped with heptanes, dissolved in DCM and the organic layer was washed with sat. aq. NaHCO3 solution and sat. NaCl solution. Purification by flash chromatography on silica gel (eluent: 35 to 45% EtOAc/hexanes which had been NH3 sparged, gradient elution) provided the title compound as the more polar isomer as a white solid: (Rf in 75% EtOAc/Hexanes=0.44).

Workup

  1. temperaturethe reaction was heated to 70° for 1.5 h
  2. customthe TFA was removed by concentration under reduced pressure
  3. customThe product was azeotroped with heptanes
  4. dissolutiondissolved in DCM
  5. washthe organic layer was washed with sat. aq. NaHCO3 solution and sat. NaCl solution
  6. customPurification by flash chromatography on silica gel (eluent: 35 to 45% EtOAc/hexanes which had been NH3 sparged, gradient elution)

Sources & evidence

ORD record
ord-42dc9fbe617e4968b940e8b5c9641c1a
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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