4-Methylmorpholine → (3-Benzylpiperidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone

HRID 874923Notes

Reaction equation

HRID 874923 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([OH:13])=O)[N:4]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:43]([CH:50]1[CH2:55][CH2:54][CH2:53][NH:52][CH2:51]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[CH2:43]([CH:50]1[CH2:55][CH2:54][CH2:53][N:52]([C:11]([C:10]2[CH:14]=[CH:15][CH:16]=[C:8]([C:5]3[N:4]=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=3)[CH:9]=2)=[O:13])[CH2:51]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 1145513-BenzylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251808543-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid

Product 1

HCID 53327767(3-Benzylpiperidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanoneYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (100 mg, 0.4 mmol) was dissolved in dry DMF (3 mL) and HATU (183 mg, 0.48 mmol) was added followed by 3-benzylpiperidine (75 mg, 0.42 mmol) and NMM (0.13 mL, 1.2 mmol) at 0° C. The reaction mixture was slowly warmed to room temperature and stirred for 8 h. The reaction mixture was then diluted with EtOAc and the organic layer was washed with water, 1.5N HCl solution and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether) to get (3-benzylpiperidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone (70 mg, yield 44%): 1H NMR (400 MHz, CDCl3) δ 8.15-8.01 (m, 2H), 7.59-7.47 (m, 2H), 7.32-7.21 (m, 2H), 7.06-6.97 (m, 3H), 4.63 (m, 1H), 3.59-3.56 (m, 1H), 2.83-2.51 (m, 4H), 1.93-1.84 (m, 3H), 1.26-1.22 (m, 2H). MS (ESI) m/z: Calculated for C22H20F3N3O2: 415.41. found: 416.2 (M+H)+.

Workup

  1. washthe organic layer was washed with water, 1.5N HCl solution and brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-c570c13a2cef4026825f6b6c6b3cc4ef
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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