Trifluoroacetic acid → HCID 68000991, compound

HRID 932057Notes

Reaction equation

HRID 932057 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-a0263c40fbad486cb2fa0eeeeaffbf8d
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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