Trifluoroacetic acid → HCID 17984356, compound

HRID 1181073Notes

Reaction equation

HRID 1181073 reaction equation
C(O)(=O)C.C([O:9][C:10](=[O:36])[CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][C:22]2[N:23]=[C:24]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[O:25][C:26]=2[CH3:27])=[CH:15][C:14]=1[CH2:34][NH2:35])(C)(C)C.[C:37]([CH:45]1[CH2:50][CH2:49][CH2:48][CH2:47][C:46]1=O)(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(O)(C(F)(F)F)=O>C1(OC)C=CC=CC=1.[Pd].O.C(Cl)Cl>[C:37]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[NH:35][CH2:34][C:14]1[CH:15]=[C:16]([O:19][CH2:20][CH2:21][C:22]2[N:23]=[C:24]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[O:25][C:26]=2[CH3:27])[CH:17]=[CH:18][C:13]=1[CH2:12][CH2:11][C:10]([OH:9])=[O:36])(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 3

HCID 6422Trifluoroacetic acidHCID 2756272-BenzoylcyclohexanoneHCID 69232911HCID 69232911, compound

Product 1

HCID 17984356HCID 17984356, compoundYield 10.2%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 7519AnisoleSolvent2×

Procedure

A solution of 3-{2-aminomethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid tert-butyl ester acetic acid salt (290 mg, 0.665 mmol, Example 1, Step B) and 2-benzoyl-cyclohexanone (161 mg, 0.797 mmol) in anisole (20 mL) was treated with a slurry of Pd/C (60 mg) in anisole (2 mL). The mixture was refluxed at 200° C. with azeotropic removal of water for 2 h and cooled to room temperature. The catalyst was filtered and a fresh slurry of Pd/C (60 mg) in anisole was added. The mixture was heated at 110° C. for 72 h and filtered through a pad of Celite. The filtrate was concentrated, purified by silica gel chromatography-(25% EtOAc/hexanes) to afford a mixture of starting material and desired tert butyl ester intermediate. The mixture was treated with TFA (1.0 ml)/CH2Cl2 (1.0 ml)/H2O (0.1 mL), stirred for 3 h, and concentrated. The residue was and purified using silica gel chromatography (MeOH/EtOAc 1/9) to give the title compound (38 mg, 10%). MS (ESI) m/z 561.3 (M+H)+.

Workup

  1. filtrationThe catalyst was filtered
  2. additiona fresh slurry of Pd/C (60 mg) in anisole was added
  3. temperatureThe mixture was heated at 110° C. for 72 h
  4. filtrationfiltered through a pad of Celite
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel chromatography-(25% EtOAc/hexanes)
  7. customto afford
  8. concentrationconcentrated
  9. custompurified

Sources & evidence

ORD record
ord-73254608e72d45afb8108c5c5da1afe5
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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