Trityl chloride → (5-Methyl-1-trityl-1H-imidazol-4-yl)methanol

HRID 1194367Notes

Reaction equation

HRID 1194367 reaction equation
C(N(CC)CC)C.[CH3:8][C:9]1[NH:13][CH:12]=[N:11][C:10]=1[CH2:14][OH:15].[C:16]1([C:22](Cl)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C)C=O.ClCCl.CO>[CH3:8][C:9]1[N:13]([C:22]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:12]=[N:11][C:10]=1[CH2:14][OH:15]

Participants

6

Reactant 3

HCID 6456Trityl chlorideHCID 8471TriethylamineHCID 1224334-hydroxymethyl-5-methyl-1H-imidazole

Product 1

HCID 11544901(5-Methyl-1-trityl-1H-imidazol-4-yl)methanolYield 50.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

230 ml (1.659 mole) of triethylamine are added in the course of 15 minutes to a solution of 100 g (0.673 mole) of 5-methyl-1H-imidazole-4-methanol in 1.5 liter of dimethylformamide maintained between 10° and 14° C. Subsequently, a solution containing 192 g (0.69 mole) of triphenylmethyl chloride in 2 liters of dimethylformamide is introduced between 8° and 11° C. The reaction mixture is stirred for 2 hours and then poured on 14 liters of ice. Stirring is continued for 1 hour, whereafter the precipitate obtained is filtered off, washed with 6 liters of water and dried. This precipitate is then again taken up in 4 liters of boiling ethanol and the insoluble material is separated by hot filtration. Thus, a first crop (19 g; M.P.: 255°-260° C.) of the desired product is recovered. The alcoholic filtrate is filtered hot on Norit, then concentrated and cooled while stirring. A second crop of the desired product crystallizes. It is filtered off, the yield being 28.3 g; M.P.: 255°-262° C. Finally, the filtrate is distilled under reduced pressure and the residue obtained is dissolved in 1 liter of a 95:5 v/v dichloromethane-methanol mixture and the solution obtained is purified by passage through a column of 1.8 kg of silica (0.2-0.5 mm) (eluent: a 80:20 v/v dichloromethane-methanol mixture). A further 72.1 g of the desired product are thus recovered. In total, 119.4 g are recovered containing practically only one of the two possible isomers in the 4- and 5-positions, namely, the 5-methyl-1-triphenylmethyl-1H-imidazole-4-methanol. The yield is 50.1% of theory. The product obtained is used as such in the following step.

Workup

  1. temperaturemaintained between 10° and 14° C
  2. additionis introduced between 8° and 11° C
  3. stirringStirring
  4. waitis continued for 1 hour, whereafter the precipitate
  5. customobtained
  6. filtrationis filtered off
  7. washwashed with 6 liters of water
  8. customdried
  9. customthe insoluble material is separated by hot filtration
  10. customThus, a first crop (19 g; M.P.: 255°-260° C.) of the desired product is recovered
  11. filtrationThe alcoholic filtrate is filtered hot on Norit
  12. concentrationconcentrated
  13. temperaturecooled
  14. stirringwhile stirring
  15. customA second crop of the desired product crystallizes
  16. filtrationIt is filtered off
  17. distillationFinally, the filtrate is distilled under reduced pressure
  18. customthe residue obtained
  19. customthe solution obtained
  20. customis purified by passage through a column of 1.8 kg of silica (0.2-0.5 mm) (eluent
  21. customA further 72.1 g of the desired product are thus recovered
  22. customIn total, 119.4 g are recovered
  23. additioncontaining practically only one of the two possible isomers in the 4- and 5-positions
  24. customThe product obtained

Sources & evidence

ORD record
ord-8a348847945f4f56a0d6f99b74a0e0f7
Source dataset
uspto-grants-1989_03
Patent number
US04814343

Reaction notes

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