Potassium Carbonate → [4-(3-Pyridyloxymethyl)-2-phenylbenzoyl]methionine hydroxamic acid

HRID 2121216Notes

Reaction equation

HRID 2121216 reaction equation
C[O:2][C:3](=O)[C@H:4]([CH2:28][CH2:29][S:30][CH3:31])[NH:5][C:6](=[O:27])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][O:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:9][C:8]=1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl.[NH2:34][OH:35].C(=O)([O-])[O-].[K+].[K+].[OH-].[K+]>CO>[N:17]1[CH:18]=[CH:19][CH:20]=[C:15]([O:14][CH2:13][C:10]2[CH:11]=[CH:12][C:7]([C:6]([NH:5][C@H:4]([C:3]([NH:34][OH:35])=[O:2])[CH2:28][CH2:29][S:30][CH3:31])=[O:27])=[C:8]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:9]=2)[CH:16]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 53962378[4-(3-Pyridyloxymethyl)-2-phenylbenzoyl]methionine methyl ester

Product 1

HCID 53762398[4-(3-Pyridyloxymethyl)-2-phenylbenzoyl]methionine hydroxamic acidYield 63.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A slurry in methanol of [4-(3-pyridyloxymethyl)-2-phenylbenzoyl]methionine methyl ester (143 mg, 0.32 mmol), prepared as in Example 234, hydroxylamine hydrochloride (26 mg, 0.37 mmol) and potassium carbonate (106 mg, 0.77 mmol) was stirred at ambient temperature for 4 hours, then a solution of potassium hydroxide in methanol (0.33 mL) was added and stirring was continued overnight at ambient temperature. The reaction mixture was filtered and the filtrate was diluted with water and taken to pH 4. The aqueous phase was extracted with 3:1 chloroform-isopropanol. The organic extract was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by prep HPLC gave [4-(3-pyridyloxymethyl)-2-phenylbenzoyl]methionine hydroxamic acid (92 mg). 1H NMR (300 MHz, DMSO-d6) δ 10.58 (br s, 1H), 8.58 (d, 1H), 8.40 (d, 1H), 8.33 (d, 1H), 7.80 (dd, 1H), 7.60 (dd, 1H), 7.50 (m, 3H), 7.36 (m, 5H), 5.35 (s, 2H), 4.20 (m, 1H), 2.12 (m, 2H), 1.98 (s, 3H), 1.70 (m, 2H). MS (APCI) m/e 452 (M+H)+.

Workup

  1. stirringstirring
  2. waitwas continued overnight at ambient temperature
  3. filtrationThe reaction mixture was filtered
  4. additionthe filtrate was diluted with water
  5. extractionThe aqueous phase was extracted with 3:1 chloroform-isopropanol
  6. extractionThe organic extract
  7. washwas washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by prep HPLC

Sources & evidence

ORD record
ord-c0592d3804d84d079b7c31d6e13fa5d3
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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