O-Cresol → 4-(4-Chlorophenyl)-2-(2-methyl-1-imidazolyl)-5-[3-(2-methylphenoxy)propyl]oxazole

HRID 47931

Reaction equation

HRID 47931 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([N:17]3[CH:21]=[CH:20][N:19]=[C:18]3[CH3:22])[O:11][C:12]=2[CH2:13][CH2:14][CH2:15][OH:16])=[CH:4][CH:3]=1.CS(Cl)(=O)=O.[C:28]1([CH3:35])[C:33](O)=[CH:32][CH:31]=[CH:30][CH:29]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([N:17]3[CH:21]=[CH:20][N:19]=[C:18]3[CH3:22])[O:11][C:12]=2[CH2:13][CH2:14][CH2:15][O:16][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH3:35])=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 335O-CresolHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 99269974-(4-Chlorophenyl)-2-(2-methyl-1-imidazolyl)-5-oxazolepropanol

Product 1

HCID 98876724-(4-Chlorophenyl)-2-(2-methyl-1-imidazolyl)-5-[3-(2-methylphenoxy)propyl]oxazoleYield 91.2%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 4-(4-chlorophenyl)-5-(3-hydroxypropyl)-2-(2-methylimidazol-1-yl)oxazole (509 g), triethylamine (254.6 mL) in toluene (4072 mL) was added dropwise methanesulfonyl chloride (136.4 mL) at not higher than 10° C. Ten minutes later, o-cresol (248.0 mL) and tetrabutylammonium bromide (25.8 g) were added to the obtained mixture and a solution of NaOH (255 g) in water (1018 mL) was further added. The mixture was heated under reflux for 1 h. After cooling, the toluene layer was separated and washed with 1N aqueous NaOH solution (4072 mL×3) and then with 5% aqueous NaCl solution. The solvent was evaporated and the obtained crystals were recrystallized from ethanol-water (9:1) to give the title compound (595.6 g, yield: 91.2%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 1 h
  3. temperatureAfter cooling
  4. customthe toluene layer was separated
  5. washwashed with 1N aqueous NaOH solution (4072 mL×3)
  6. customThe solvent was evaporated
  7. customthe obtained crystals were recrystallized from ethanol-water (9:1)

Sources & evidence

ORD record
ord-8c6af652983a4487ad552939860ff0e2
Source dataset
uspto-grants-2004_03
Patent number
US06699995B1

Linked notes

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