Bromoacetonitrile → 4-[4-(3-Chloro-4-fluoro-phenyl)-1-cyanomethyl-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1685159Notes

Reaction equation

HRID 1685159 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Br[CH2:30][C:31]#[N:32]>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:30][C:31]#[N:32])[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11534BromoacetonitrileHCID 14798Sodium HydroxideHCID 178451793HCID 178451793, compound

Product 1

HCID 672655344-[4-(3-Chloro-4-fluoro-phenyl)-1-cyanomethyl-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 76%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Combine 4-[4-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (2.55 mmol; 969 mg), tetra-N-butylammonium bromide (0.26 mmol; 82 mg), 50 wt % aq sodium hydroxide (8.42 mmol; 0.45 mL) and DCM (25 mL). Add bromoacetonitrile (5.11 mmol; 0.36 mL) dropwise over 10 min. Stir 45 min and dilute with DCM, wash with brine, 50% saturated aqueous sodium chloride solution, dry over MgSO4, filter and evaporate. Purify over 150 g silica gel with 20% EA/DCM to provide the title compound (812 mg; 76%). MS (ES): m/z=419 (M+H).

Workup

  1. washwash with brine, 50% saturated aqueous sodium chloride solution
  2. dry with materialdry over MgSO4
  3. filtrationfilter
  4. customevaporate
  5. customPurify over 150 g silica gel with 20% EA/DCM

Sources & evidence

ORD record
ord-1b2446a50e9a4ce193f058f9724904bb
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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