Ammonium Chloride → (2-Methyl-1-trityl-1H-imidazol-4-YL)(1-(trifluoromethyl)cyclopropyl)methanone

HRID 216312Notes

Reaction equation

HRID 216312 reaction equation
C([Mg]Br)C.I[C:6]1[N:7]=[C:8]([CH3:30])[N:9]([C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:10]=1.CON(C)[C:34]([C:36]1([C:39]([F:42])([F:41])[F:40])[CH2:38][CH2:37]1)=[O:35].[Cl-].[NH4+]>C(Cl)Cl>[CH3:30][C:8]1[N:9]([C:11]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:10]=[C:6]([C:34]([C:36]2([C:39]([F:42])([F:41])[F:40])[CH2:38][CH2:37]2)=[O:35])[N:7]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 109504214-iodo-2-methyl-1-trityl-1H-imidazoleHCID 57785368N-methoxy-N-methyl-1-(trifluoromethyl)cyclopropane-1-carboxamideHCID 178418443HCID 178418443, compound

Product 1

HCID 68667421(2-Methyl-1-trityl-1H-imidazol-4-YL)(1-(trifluoromethyl)cyclopropyl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

Ethylmagnesium bromide (3 M solution in diethyl ether) (633 mL, 1.9 mol) was added over 1 h to a 5° C. solution of 4-iodo-2-methyl-1-trityl-1H-imidazole (855 g, 1.9 mol) in methylene chloride (8 L). After stirring at 5° C. for 30 min, the reaction mixture was allowed to warm to ca. 12° C. and a solution of N-methoxy-N-methyl-1-(trifluoromethyl)cyclopropanecarboxamide (355 g, 1.8 mol) in methylene chloride (2 L) was added over 1 h. After stirring at ambient temperature overnight, the reaction mixture was poured into saturated aqueous ammonium chloride. The organic phase was washed with saturated aqueous sodium bicarbonate, dried (magnesium sulfate) and concentrated in vacuo. The residue was dissolved in a minimal volume of ether and crashed out with heptane. After stirring in heptane (ca. 3 L) for 1 h, solid was collected by filtration, washing with heptane to afford (2-methyl-1-trityl-1H-imidazol-4-yl)[1-(trifluoromethyl)cyclopropyl]methanone.

Workup

  1. temperatureto warm to ca. 12° C.
  2. stirringAfter stirring at ambient temperature overnight
  3. washThe organic phase was washed with saturated aqueous sodium bicarbonate
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in a minimal volume of ether
  7. stirringAfter stirring in heptane (ca. 3 L) for 1 h
  8. filtrationsolid was collected by filtration
  9. washwashing with heptane

Sources & evidence

ORD record
ord-a45aecc4ffd4400686f7dd1fbd85fe35
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Reaction notes

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