Trifluoroacetic acid → HCID 86271001, compound

HRID 2170214Notes

Reaction equation

HRID 2170214 reaction equation
[CH:1]1([O:7][C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=2[C:15]2[N:16](COCC[Si](C)(C)C)[C:17]([CH3:30])=[C:18]3[C:23]=2[CH:22]=[C:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[NH:20][C:19]3=[O:29])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O.C([O-])(=O)C.[K+]>ClCCl>[CH:1]1([O:7][C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=2[C:15]2[NH:16][C:17]([CH3:30])=[C:18]3[C:23]=2[CH:22]=[C:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[NH:20][C:19]3=[O:29])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 517044Potassium AcetateHCID 90387431HCID 90387431, compound

Product 1

HCID 86271001HCID 86271001, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 48a (0.020 g, 0.037 mmol) in dichloromethane was added TFA (2.84 μL, 0.037 mmol). The reaction mixture was stirred at ambient temperature for 1 hour and then concentrated by rotary evaporation. The residue was concentrated down from toluene (2×) then taken up in methanol/tetrahydrofuran. Potassium acetate (0.145 g, 1.474 mmol) was added, and the reaction mixture was heated at reflux for 2 hours. The reaction mixture was concentrated by rotary evaporation. The residue was partitioned between ethyl acetate and water. The layers were separated, and the organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography (silica gel, 20-80% ethyl acetate in hexanes) to give the title compound (0.010 g, 66% yield). 1H NMR (300 MHz, DMSO-d6) δ 12.01 (s, 1 H), 9.29 (s, 1 H), 7.18 (s, 1 H), 6.93-7.09 (m, 3 H), 4.15-4.21 (m, 1 H), 4.12 (q, J=7.12 Hz, 2 H), 2.49 (s, 3 H), 1.69-1.75 (m, 2 H), 1.38-1.45 (m, 2 H), 1.20-1.33 (m, 2 H), 1.13 (t, J=7.02 Hz, 3 H), 1.07-1.18 (m, 4 H). MS (ESI+) m/z 413.1 (M+H)+.

Workup

  1. concentrationconcentrated by rotary evaporation
  2. concentrationThe residue was concentrated down from toluene (2×)
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 2 hours
  5. concentrationThe reaction mixture was concentrated by rotary evaporation
  6. customThe residue was partitioned between ethyl acetate and water
  7. customThe layers were separated
  8. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by flash chromatography (silica gel, 20-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f18976341a54458b95c8dcec940b7858
Source dataset
uspto-grants-2015_06
Patent number
US09050346B2

Reaction notes

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