1-Hydroxybenzotriazole → 5-Phenyl-isoxazole-3-carboxylic acid {2-[4-(2-bromo-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093583Notes

Reaction equation

HRID 1093583 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]([NH:14][CH2:15][C:16]([OH:18])=O)=[O:13])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.FC(F)(F)C(O)=O.[Br:57][C:58]1[CH:70]=[CH:69][CH:68]=[CH:67][C:59]=1[O:60][CH:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>CN(C=O)C.O>[Br:57][C:58]1[CH:70]=[CH:69][CH:68]=[CH:67][C:59]=1[O:60][CH:61]1[CH2:66][CH2:65][N:64]([C:16](=[O:18])[CH2:15][NH:14][C:12]([C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:11][N:10]=2)=[O:13])[CH2:63][CH2:62]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 433543392-[(5-Phenyl-1,2-oxazol-3-yl)formamido]acetic acidHCID 66591525HCID 66591525, compound

Product 1

HCID 442355005-Phenyl-isoxazole-3-carboxylic acid {2-[4-(2-bromo-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (72.5 mg, 0.00026 mol) in DMF (1.5 mL) was added DIPEA (0.166 g, 0.00128 mol), HOBt (43.3 mg, 0.00032 mol) and EDCI.HCl (61.5 mg, 0.00032 mol) at ambient temperature. After 2 minutes 4-(2bromo-phenoxy)-piperidine trifluoroacetate (0.1 g, 0.00027 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel, 60-120 mesh (40% ethyl acetate in hexane) to afford 0.044 g (35%) of 5-phenyl-isoxazole-3-carboxylic acid {2-[4-(2-bromo-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 484.08 (M+1)+, 77.84%, 1H NMR (DMSO-d6): δ 8.63 (t, 1H), 7.98 (m, 2H), 7.6 (m, 4H), 7.4 (m, 2H), 7.2 (m, 1H), 6.9 (t, 1H), 4.8 (s, 1H), 4.3 (m, 2H), 3.5 (m, 4H), 1.5 (m, 4H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-8f3fb06508e84bb0bea6d05801accd78
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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