Methanol → 1-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-4-carboxylic acid methyl ester

HRID 557777Notes

Reaction equation

HRID 557777 reaction equation
[CH3:1][OH:2].[C:3]1([C:9]2[O:10][C:11]([C:17]([F:20])([F:19])[F:18])=[C:12]([C:14](Cl)=[O:15])[N:13]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1(C2O[C:29]([C:35](F)(F)F)=[C:30]([C:32](O)=O)[N:31]=2)C=CC=CC=1.[C:39](Cl)(=[O:43])[C:40](Cl)=O.[CH2:45]([N:47]([CH2:50][CH3:51])[CH2:48][CH3:49])[CH3:46]>[Pd].C(Cl)Cl.C1COCC1>[CH3:1][O:2][C:39]([CH:40]1[CH2:49][CH2:48][N:47]([C:50]2[CH:35]=[CH:29][C:30]([NH:31][C:14]([C:12]3[N:13]=[C:9]([C:3]4[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=4)[O:10][C:11]=3[C:17]([F:20])([F:19])[F:18])=[O:15])=[CH:32][CH:51]=2)[CH2:45][CH2:46]1)=[O:43]

Participants

9

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acidHCID 860328062-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl chloride

Product 1

HCID 576520321-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

The yellow solid prepared above (463 mg, 1.75 mmol) was dissolved into methanol (25 ml) and THF (5 mL). To this solution was added 10% palladium on carbon (100 mg) and the mixture was hydrogenated at 50 psi for 2 hrs. The mixture was filtered and solvents were evaporated to give a purple residue. This material was dissolved in methylene chloride (5 mL) containing triethyl amine (0.4 mL) and the solution was added to a methylene chloride solution of 2-phenyl-5-trifluoromethyloxazole-4-carbonyl chloride which was prepared from 2-phenyl-5-trifluoromethyloxazole-4-carboxylic acid (450.7 mg, 1.753 mmol) and oxalyl chloride. The mixture was stirred at r.t for 3 hrs and solvents were evaporated. The residue was extracted with ethyl acetate and diluted hydrochloric acid and solvents were evaporated. The resulting mixture was purified through a flash column chromatography using ethyl acetate and hexanes (1:1 ratio) to give a white solid as 1-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-4-carboxylic acid methyl ester (650 mg). 1H-NMR is consistent with the structure. LC-MS indicated a single peak (Rf=3.85 min). LRMS for C24H22F3N3O4 (m/e) calcd 473.16, obsd 474.3 (M+1).

Workup

  1. customThe yellow solid prepared above (463 mg, 1.75 mmol)
  2. filtrationThe mixture was filtered
  3. customsolvents were evaporated
  4. customto give a purple residue
  5. customsolvents were evaporated
  6. extractionThe residue was extracted with ethyl acetate and diluted hydrochloric acid and solvents
  7. customwere evaporated
  8. customThe resulting mixture was purified through a flash column chromatography

Sources & evidence

ORD record
ord-abfa0006e8a44eba92e443bb4b7fbcae
Source dataset
uspto-grants-2011_11
Patent number
US08058299B2

Reaction notes

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