Water → HCID 12790771, compound

HRID 1660147Notes

Reaction equation

HRID 1660147 reaction equation
[OH-].[Na+].O.[Cl:4][C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[CH:12]([OH:19])[CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[CH:15]1.Cl.Cl[CH2:22][C:23]1[N:24]=[C:25]([CH3:28])[S:26][CH:27]=1>[Cl-].C([N+](C)(C)C)C1C=CC=CC=1.O1CCCC1>[ClH:4].[Cl:4][C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[CH:12]([O:19][CH2:22][C:23]1[N:24]=[C:25]([CH3:28])[S:26][CH:27]=1)[CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[CH:15]1.[Cl:4][C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[CH:12]([O:19][CH2:22][C:23]1[N:24]=[C:25]([CH3:28])[S:26][CH:27]=1)[CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[CH:15]1

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 32238(+-)-alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanolHCID 27342034-(Chloromethyl)-2-methyl-1,3-thiazole--hydrogen chloride (1/1)

Product 2

HCID 12790771HCID 12790771, compoundHCID 131712620HCID 131712620, compound

Reagents, catalysts & solvents 2

HCID 5963Benzyltrimethylammonium chlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

In a three-necked flask, fitted with stirrer, reflux condenser and gas inlet tube, 44 g of sodium hydroxide (1.1 mol) and 50 ml of water are introduced. While passing nitrogen through the flask, the solution is cooled to 45° and then 11.6 g of (1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol (0.045 mol) [prepared by the method of J. Med. Chem. 12, 784, (1969)], 0.75 g of benzyltrimethylammonium chloride and 150 ml of tetrahydrofuran are added. To the mixture, which is warmed to 50°, 8.3 g of 4-chloromethyl-2-methylthiazole, hydrochloride (0.045 mol) are added and the mixture is stirred vigorously for two hours at 60°. The filtered biphasic solution is transferred into a separating funnel, the lower aqueous sodium hydroxide is extracted with 10 ml of tetrahydrofuran. The combined tetrahydrofuran layers are treated with charcoal and after drying with sodium sulphate, the solvent is evaporated in vacuo. The resulting oily product, dissolved in 250 ml of ether, is allowed to stand overnight in a refrigerator, by which operation unreacted 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol is separated. Filtering off and addition of ethereal hydrochloric acid to the clear ethereal solution yields the hydrochloride of 4-[[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy]methyl]-2-methylthiazole. Yield: 12.8 g (71%). Recrystallization from acetonitrile gives a hydrochloride with the m.p. of 194°-196° C.

Workup

  1. customIn a three-necked flask, fitted with stirrer
  2. temperaturereflux condenser and gas inlet tube
  3. temperaturethe solution is cooled to 45°
  4. temperatureTo the mixture, which is warmed to 50°
  5. customThe filtered biphasic solution is transferred into a separating funnel
  6. extractionthe lower aqueous sodium hydroxide is extracted with 10 ml of tetrahydrofuran
  7. additionThe combined tetrahydrofuran layers are treated with charcoal
  8. dry with materialafter drying with sodium sulphate
  9. customthe solvent is evaporated in vacuo
  10. dissolutionThe resulting oily product, dissolved in 250 ml of ether
  11. waitto stand overnight in a refrigerator, by which operation unreacted 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol
  12. customis separated
  13. filtrationFiltering off
  14. additionaddition of ethereal hydrochloric acid to the clear ethereal solution

Sources & evidence

ORD record
ord-cbe69acb0aef4241b2d65d2ed05803e4
Source dataset
uspto-grants-1981_12
Patent number
US04307105

Reaction notes

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