Coumaranone → HCID 86666753, compound

HRID 1804633Notes

Reaction equation

HRID 1804633 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3](=O)[CH2:2]1.[N:11]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(=O)(O)[O-].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[H][H]>C1COCC1.[Pd].CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CO>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]([N:14]2[CH2:13][CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15]2)[CH2:2]1

Participants

10

Reactant 5

HCID 23556CoumaranoneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 86666753HCID 86666753, compound

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 80 mg (0.47 mmol) of the title compound from Step C and 87 mg (0.47 mmol) tert-butyl 1-piperazine-carboxylate in 20 ml THF was added 39 mg (0.47 mmol) sodium bicarbonate and 0.27 ml (0.93 mmol) of titanium(IV) isopropoxide. The reaction was stirred at RT for 30 min, and was heated at 70° C. for 4 h. The reaction was cooled down to ambient temperature and 200 mg (0.93 mmol) of sodium triacetoxyborohydride was added into the mixture. The reaction was continued by stirring at ambient temperature overnight. The reaction was quenched with methanol and concentrated. The reaction was partitioned between ethyl acetate and water, the organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated in vacuo. The residue was purified by reverse-phase HPLC (TMC Pro-Pac C18; 10-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient) to give the intermediate with double bond. To the above intermediate was added 20 ml methanol and 5 mg of 10% Palladium on carbon. Hydrogenation was carried out under the hydrogen gas balloon for 4 hr. The reaction mixture was filtered and the filtrate was concentrated to afford the title compound. LC/MS: (M-56): 249.6

Workup

  1. temperaturewas heated at 70° C. for 4 h
  2. temperatureThe reaction was cooled down to ambient temperature
  3. stirringby stirring at ambient temperature overnight
  4. customThe reaction was quenched with methanol
  5. concentrationconcentrated
  6. customThe reaction was partitioned between ethyl acetate and water
  7. washthe organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue was purified by reverse-phase HPLC (TMC Pro-Pac C18; 10-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient)
  12. customto give the intermediate with double bond
  13. filtrationThe reaction mixture was filtered
  14. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-d9586919c5834b098cf304e7779cfbda
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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