Trityl chloride → 1-(Triphenylmethyl)-4-[2-(trifluoroacetamido)-1-ethyl]imidazole

HRID 2408301Notes

Reaction equation

HRID 2408301 reaction equation
Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]=[CH:9][NH:8][CH:7]=1.C(N(CC)CC)C.C(O[C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])C.[C:27](Cl)([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CO.O.C(Cl)(Cl)Cl>[F:25][C:22]([F:23])([F:24])[C:21]([NH:3][CH2:4][CH2:5][C:6]1[N:10]=[CH:9][N:8]([C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:7]=1)=[O:26]

Participants

8

Reactant 4

HCID 6456Trityl chlorideHCID 8471Triethylamine2×HCID 9794Ethyl trifluoroacetateHCID 178478691HCID 178478691, compound

Product 1

HCID 110377171-(Triphenylmethyl)-4-[2-(trifluoroacetamido)-1-ethyl]imidazole

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

Histamine dihydrochloride (20.47 g; 0.111 mol) and triethylamine (48 mL; 0.345 mol) in absolute methanol (400 mL) were stirred at room temperature for 10 min. Trifluoroacetic acid ethyl ester (14.6 mL; 0.122 mol) in methanol (30 mL) was added dropwise over 30 min at 0° C. Reaction mixture was stirred for 3.5 hrs at room temperature and then it was evaporated to dryness in vacuo. The residue was dissolved in dichlormethane (450 mL) and triethylamine (31 mL; 0.222 mol) was added. Then trityl chloride (34.1 g; 0.122 mol) was added piecewise and mixture was stirred over night at room temperature. Chloroform (400 mL) and water (600 mL) were poured into reaction mixture. Aqueous layer was separated and extracted with chloroform (3×400 mL). The combined organic layers were dried over anhydrous magnesium sulfate. Solvent was removed and the beige solid was triturated with hexanes (1000 mL). Suspension was filtered to yield 2,2,2-trifluoro-N-[2-(1-trityl-1H-imidazol-4-yl)-ethyl]-acetamide as white solid.

Workup

  1. customReaction mixture
  2. customit was evaporated to dryness in vacuo
  3. dissolutionThe residue was dissolved in dichlormethane (450 mL)
  4. stirringmixture was stirred over night at room temperature
  5. customAqueous layer was separated
  6. extractionextracted with chloroform (3×400 mL)
  7. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  8. customSolvent was removed
  9. customthe beige solid was triturated with hexanes (1000 mL)
  10. filtrationSuspension was filtered

Sources & evidence

ORD record
ord-1b154d508fac4c74bb135ac0b99cdb11
Source dataset
uspto-grants-2014_08
Patent number
US08815802B2

Reaction notes

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