Trifluoroacetic acid → HCID 45275679, compound

HRID 1622380Notes

Reaction equation

HRID 1622380 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][C:11]([CH3:19])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.FC(F)(F)C(O)=O.[Cl:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([Cl:35])C=1Cl.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C(Cl)Cl.CN1C(=O)CCC1.C1(C)C=CC=CC=1>[Cl:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([Cl:35])[C:1]=1[N:8]1[CH2:9][CH2:10][C:11]([CH3:19])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][CH2:13]1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 37865313,4,5-TrichloropyridineHCID 162182761-tert-Butyl 4-ethyl 4-methylpiperidine-1,4-dicarboxylate

Product 1

HCID 45275679HCID 45275679, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
220 °C

Procedure

To a solution of ethyl N-Boc-4-methylpiperidine-4-carboxylate (130 mg, 0.47 mmol) in CH2Cl2 (8 mL) was added trifluoroacetic acid (0.86 mL, 11 mmol) and the reaction stirred at r.t. for 2 hr before evaporation and aziotrope with toluene (2×25 ml). The crude was dissolved in NMP (4.3 ml) and 3,4,5-trichloropyridine (135 mg, 0.74 mmol) was added followed by triethylamine (0.42 mL, 3.0 mmol) and the mixture was heated in a microwave reactor at 220° C. for 60 min. The mixture was poured into a saturated solution of sodium hydrogen carbonate (50 mL) and extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (2×50 mL), brine (50 mL), dried (MgSO4) and concentrated under reduced pressure to give a crude pale brown/orange oil (175 mg). The crude product was purified by flash column chromatography on silica gel (cyclohexane, EtOAc, 99:1-88:12, biotage 25+S) to furnish the title compound as a clear colourless oil (85 mg, 56%), LC-MS (ESI, 4 min) Rt 3.36 min, m/z 317 (100%, [M+H]+); m/z (ESI) C14H18N2O2Cl2 requires 316.0745, found [M+H]+ 316.0745.

Workup

  1. extractionextracted with EtOAc (2×100 mL)
  2. washThe combined organic extracts were washed with water (2×50 mL), brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customto give a crude pale brown/orange oil (175 mg)
  6. customThe crude product was purified by flash column chromatography on silica gel (cyclohexane, EtOAc, 99:1-88:12, biotage 25+S)

Sources & evidence

ORD record
ord-f0697b95f1e4410695c2f46e016dd0b7
Source dataset
uspto-grants-2014_07
Patent number
US08778925B2

Reaction notes

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