Trityl chloride → HCID 11037717, compound

HRID 240295Notes

Reaction equation

HRID 240295 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 11037717HCID 11037717, compound

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-d7e4fff13c914cf39bfb164b1bd21637
Source dataset
uspto-grants-2014_02
Patent number
US08648041B2

Reaction notes

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