Methyl triflate → dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate

HRID 551141Notes

Reaction equation

HRID 551141 reaction equation
ClC1C=CC=C(F)C=1C(NCC1(CC2CC2)CCNCC1)=O.[F:23][C:24]([F:30])([F:29])[S:25]([O-:28])(=[O:27])=[O:26].[CH3:31][C:32]1[N:33](S(N2C=CN=C2C)(=O)=O)[CH:34]=[CH:35][N+:36]=1[CH3:37].O(C)S(C(F)(F)F)(=O)=O>C(#N)C.C(Cl)Cl>[F:23][C:24]([F:30])([F:29])[S:25]([O-:28])(=[O:27])=[O:26].[CH3:31][C:32]1[NH:33][CH:34]=[CH:35][N+:36]=1[CH3:37]

Participants

6

Reactant 3

HCID 9526Methyl triflateHCID 108728322,3-dimethyl-1-[(2-methyl-1H-imidazol-1-yl)sulfonyl]-1H-imidazol-3-ium trifluoromethanesulfonateHCID 579311812-Chloro-6-fluoro-n-{[4-cyclopropylmethylpiperidin-4-yl]methyl}benzamide

Product 1

HCID 129773273dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-chloro-6-fluoro-N-{[4-cyclopropylmethylpiperidin-4-yl]methyl}benzamide (I-4) in acetonitrile (2.5 mL) was added to a solution of 2,3-dimethyl-1-[(2-methyl-1H-imidazol-1-yl)sulfonyl]-1H-imidazol-3-ium trifluoromethanesulfonate (for synthesis see J. Org. Chem., 2003, 68, 115) (361 mg, 0.925 mmol) in acetonitrile (2 mL) The yellow solution was stirred at room temperature for 12 h then the solvent removed in vacuo. Biotage chromatography (2% methanol-DCM) afforded 2-chloro-N-{[4-cyclopropylmethyl)-1-[(2-methyl-1H-imidazol-1-ylsulfonyl)]-piperidin-4-yl]methyl}6-fluoro-benzamide (144 mg) that was directly methylated. A solution of methyl triflate (0.031 mL, 0.27 mmol) in DCM (1 mL) was added dropwise to a stirred solution of 2-chloro-N-{[4-cyclopropylmethyl)-1-[(2-methyl-1H-imidazol-1-ylsulfonyl)]-piperidin-4-yl]methyl}6-fluoro-benzamide (118 mg) in DCM (2 mL) cooled in an ice bath. The solution was stirred in an ice bath for 1.5 h then the volatile components removed in vacuo to leave 1-{[4-{[2-chloro-6-fluorobenzoyl)amino]methyl}-4-(cyclopropylmethyl)piperidin-1-yl]sulfonyl}-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate (I-5) that was used in the next step without further purification. MS 483 (M+).

Workup

  1. customthe solvent removed in vacuo
  2. customBiotage chromatography (2% methanol-DCM) afforded 2-chloro-N-{[4-cyclopropylmethyl)-1-[(2-methyl-1H-imidazol-1-ylsulfonyl)]-piperidin-4-yl]methyl}6-fluoro-benzamide (144 mg) that
  3. temperaturecooled in an ice bath
  4. stirringThe solution was stirred in an ice bath for 1.5 h
  5. customthe volatile components removed in vacuo

Sources & evidence

ORD record
ord-dd0feae95eb94db7827eebb1616ef1b7
Source dataset
uspto-grants-2011_05
Patent number
US07947714B2

Reaction notes

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