Hydrochloric Acid → HCID 66911497, compound

HRID 1967436Notes

Reaction equation

HRID 1967436 reaction equation
O1CCO[CH:2]1[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:7]=1[C@H:14]([C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=1)[CH2:15][NH:16][C:17](=[O:20])[O:18][CH3:19].Cl>O1CCOCC1.C(O)C.FC(F)(F)C(O)=O.[Pd]>[CH3:13][O:12][C:10]1[CH:11]=[C:6]2[C:7]([C@H:14]([C:21]3[CH:30]=[CH:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH:22]=3)[CH2:15][N:16]([C:17]([O:18][CH3:19])=[O:20])[CH2:2]2)=[CH:8][CH:9]=1

Participants

7

Reactant 2

HCID 313Hydrochloric AcidHCID 66911546HCID 66911546, compound

Product 1

HCID 66911497HCID 66911497, compoundYield 60%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6422Trifluoroacetic acidSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of Compound 24 (0.10 g, 0.25 mmol) in 1,4-dioxane (10 mL) at 0° C. was added concentrated HCl (0.8 mL). The reaction solution was stirred at room temperature for 20 min, and then quenched with aqueous sodium bicarbonate and extracted with dichloromethane (2×). The combined organic extract was dried over sodium sulfate and concentrated in vacuo. The residue obtained was dissolved in a mixture of ethanol (30 mL) and trifluoroacetic acid (2 mL). Palladium on carbon (105 mg) was added and the reaction mixture was shaken under hydrogen (25 psi) for 15 min, then filtered through a pad of celite and concentrated in vacuo. The residue was dissolved in dichloromethane and the resulting solution was washed with aqueous sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo. Purification by preparative thin layer chromatography (hexanes/ethyl acetate 75:25) provided Compound 25 (52 mg, 60%) as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.82-7.74 (m, 3H), 7.62-7.51 (m, 1H), 7.47-7.44 (m, 2H), 7.24 (d, J=9.0 Hz, 1H), 6.85 (d, J=8.5 Hz, 1H), 6.80-6.68 (m, 2H), 4.83-4.60 (m, 2H), 4.40-3.90 (m, 2H), 3.81 (s, 3H), 3.76-3.42 (m, 4H); ESI MS m/z 348 [M+H]+.

Workup

  1. customquenched with aqueous sodium bicarbonate
  2. extractionextracted with dichloromethane (2×)
  3. extractionThe combined organic extract
  4. dry with materialwas dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. stirringthe reaction mixture was shaken under hydrogen (25 psi) for 15 min
  8. filtrationfiltered through a pad of celite
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in dichloromethane
  11. washthe resulting solution was washed with aqueous sodium bicarbonate
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customPurification by preparative thin layer chromatography (hexanes/ethyl acetate 75:25)

Sources & evidence

ORD record
ord-6781fbd36d8e4602ae3b3f0e2306b4cf
Source dataset
uspto-grants-2013_04
Patent number
US08420811B2

Reaction notes

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