Felbinac → HCID 10269797, compound

HRID 499718Notes

Reaction equation

HRID 499718 reaction equation
[N+](C1C=CC=CC=1O)([O-])=O.[C:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=O)=[CH:13][CH:12]=1.CC(C)N=C=NC(C)C.[CH3:36][N:37]1[CH2:42][CH2:41][CH:40]([NH:43][CH3:44])[CH2:39][CH2:38]1.[Cl:45]CC(Cl)C>CN(C=O)C>[ClH:45].[C:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:12]=[CH:13][C:14]([CH2:17][C:18]([N:43]([CH3:44])[CH:40]2[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]2)=[O:20])=[CH:15][CH:16]=1

Participants

7

Reactant 5

HCID 3332FelbinacHCID 65641,2-Dichloropropane3×HCID 69472-NitrophenolHCID 12734DiisopropylcarbodiimideHCID 5663231-Methyl-4-(methylamino)piperidine

Product 1

HCID 10269797HCID 10269797, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the polymeric nitrophenol (1.5 g, approx. 1 mmol) was added a filtered solution of 4-biphenylylacetic acid (1.10 g, 5.18 mmol) in a mixture of 1,2-dichloropropane (18 ml) and DMF (2 ml), followed by the addition of a solution of DIC (0.63 g, 4.99 mmol) in 1,2-dichloropropane (5 ml). The mixture was shaken at room temperature for 15 hours, filtered, and the polymer was extensively washed with DCM, DMF, and 1,2-dichloropropane. To the polymer was added 1,2-dichloropropane (5 ml) and a solution of 1-methyl-4-methylaminopiperidine (0.10 g, 0.78 mmol) in 1,2-dichloropropane (10 ml). The resulting mixture was shaken at room temperature for 21 hours and then at 60° C. for one hour, filtered, and the polymer was carefully washed with DCM and methanol. The combined filtrates were concentrated to yield the crude product, which was purified by column chromatography (silicagel, gradient elution with DCM/methanol). The amine was mixed with ethanol and 1 molar aqueous hydrochloric acid, concentrated, and the residual hydrochloride was recrystallized from acetone. 120 mg (42%) of the title compound was obtained.

Workup

  1. filtrationfiltered
  2. washthe polymer was extensively washed with DCM, DMF, and 1,2-dichloropropane
  3. additionTo the polymer was added 1,2-dichloropropane (5 ml)
  4. stirringThe resulting mixture was shaken at room temperature for 21 hours
  5. waitat 60° C. for one hour
  6. filtrationfiltered
  7. washthe polymer was carefully washed with DCM and methanol
  8. concentrationThe combined filtrates were concentrated
  9. customto yield the crude product, which
  10. customwas purified by column chromatography (silicagel, gradient elution with DCM/methanol)
  11. additionThe amine was mixed with ethanol and 1 molar aqueous hydrochloric acid
  12. concentrationconcentrated
  13. customthe residual hydrochloride was recrystallized from acetone

Sources & evidence

ORD record
ord-52d7dd6105434f9b870516259c65cab8
Source dataset
uspto-grants-2010_08
Patent number
US07767695B2

Reaction notes

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