5-(2-Benzyloxy-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide → 5-(2-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093646Notes

Reaction equation

HRID 1093646 reaction equation
[Cl:1][C:2]1[CH:39]=[CH:38][CH:37]=[CH:36][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:35])[CH2:12][NH:13][C:14]([C:16]2[CH:20]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27]CC3C=CC=CC=3)[O:18][N:17]=2)=[O:15])[CH2:7][CH2:6]1>CO.[Pd]>[Cl:1][C:2]1[CH:39]=[CH:38][CH:37]=[CH:36][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:35])[CH2:12][NH:13][C:14]([C:16]2[CH:20]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[OH:27])[O:18][N:17]=2)=[O:15])[CH2:7][CH2:6]1

Participants

4

Reactant 1

HCID 578744145-(2-Benzyloxy-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

Product 1

HCID 1359151875-(2-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 43.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of 5-(2-benzyloxy-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide (0.153 g, 0.00028 mole) in methanol (50 mL) was added 10% Pd/C (0.03 g) and the resulting mixture was stirred under an atmosphere of hydrogen for 3 hours. The mixture was then filtered through celite, the celite was washed with methanol and the organic layers were concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to afford 0.055 g (43%) of 5-(2-hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 456.12 (M+1)+, 98.75%. 1H NMR (DMSO-d6): δ 10.8 (s, 1H), 8.7 (t, 1H), 7.8 (d, 1H), 7.4 (d, 1H), 7.24 (m, 3H), 7.12 (s, 1H), 7.04 (d, 1H), 6.92 (t, 2H), 4.7 (m, 1H), 4.2 (d, 2H), 3.7 (m, 2H), 3.4 (m, 2H), 1.9 (m, 2H), 1.6 (m, 2H).

Workup

  1. filtrationThe mixture was then filtered through celite
  2. washthe celite was washed with methanol
  3. concentrationthe organic layers were concentrated under reduced pressure
  4. customThe resulting residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-75102939241945fe9396244bb638a950
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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