Potassium Carbonate → 3-[5-(4-Acetyl-3-hydroxy-2-methyl-phenoxymethyl)-[1,2,4]oxadiazol-3-ylmethyl]-benzoic acid

HRID 1161165Notes

Reaction equation

HRID 1161165 reaction equation
[OH:1][C:2]1[C:7]([CH3:8])=[C:6]([O:9][CH2:10][C:11]2[O:15][N:14]=[C:13]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19](I)[CH:18]=3)[N:12]=2)[CH:5]=[CH:4][C:3]=1[C:24](=[O:26])[CH3:25].S([O-])(OCCCCCCCCCCCC)(=O)=O.[Na+].[C:45]([O-])([O-:47])=[O:46].[K+].[K+].[C]=O>C1(C)C=CC=CC=1.O.CC#N.CC#N.Cl[Pd]Cl.C(O)CCC>[C:24]([C:3]1[CH:4]=[CH:5][C:6]([O:9][CH2:10][C:11]2[O:15][N:14]=[C:13]([CH2:16][C:17]3[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=3)[C:45]([OH:47])=[O:46])[N:12]=2)=[C:7]([CH3:8])[C:2]=1[OH:1])(=[O:26])[CH3:25]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 3423265Sodium Lauryl SulfateHCID 666996211-{2-Hydroxy-4-[3-(3-iodo-benzyl)-[1,2,4]oxadiazol-5-ylmethoxy]-3-methyl-phenyl}-ethanoneHCID 178418416HCID 178418416, compound2×

Product 1

HCID 578844573-[5-(4-Acetyl-3-hydroxy-2-methyl-phenoxymethyl)-[1,2,4]oxadiazol-3-ylmethyl]-benzoic acidYield 65%

Reagents, catalysts & solvents 4

HCID 1140TolueneCatalystHCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 2631-ButanolSolventHCID 962WaterSolvent

Procedure

Combine 1-{2-hydroxy-4-[3-(3-iodo-benzyl)-[ 1,2,4]oxadiazol-5-ylmethoxy]-3-methyl-phenyl}-ethanone (150 mg, 0.32 mmol), sodium dodecyl sulfate (300 mg, 1.0 mmol), K2CO3 (45 mg, 0.32 mmol), 1-butanol (200 μL), and 1 drop of toluene in H2O (4 mL) in a pressure vessel, then degas with Ar for 5 min. Add PdCl2(MeCN)2 (18 mg, 0.07 mmol) to the reaction mixture. Exchange the atmposphere with carbon monoxide and heat the mixture to 70° C. under 20 psig of carbon monoxide. The reaction is heated until complete. Filter the black mixture through celite. Acidify the filtrate with 5 N hydrochloric acid to pH=1. A milky white mixture forms. Add a small amount of methanol to induce crystallization Collect the crystals by filtration to give the title compound (79 mg, 65%). 1H NMR (DMSO-d6) δ 12.99 (s, 1H), 12.79 (s, 1H), 7.86 (m, 1H), 7.79 (m, 2H), 7.52 (m, 1H), 7.42 (dd, 1H), 6.67 (d, 1H), 5.60 (s, 2H), 4.19 (s, 2H), 2.55 (s, 3H), 1.99 (s, 3H). LC-MS (m/e): 381 (M−1).

Workup

  1. temperatureThe reaction is heated until complete
  2. filtrationFilter the black mixture through celite
  3. additionAdd a small amount of methanol
  4. customcrystallization
  5. customCollect the crystals
  6. filtrationby filtration

Sources & evidence

ORD record
ord-00d60ce658d04a1eb59ba4d38f86a69e
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

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