Diethyl Ether → HCID 66650300, compound

HRID 419714Notes

Reaction equation

HRID 419714 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([C:9]2[N:10]=[C:11]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[NH:12][CH:13]=2)[CH:6]=[CH:7][CH:8]=1.[CH2:29](OCC)C.[H-].[Na+].CI>C1COCC1>[CH3:29][N:12]1[CH:13]=[C:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:27])([F:1])[F:28])[CH:4]=2)[N:10]=[C:11]1[CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178451790HCID 178451790, compound

Product 1

HCID 66650300HCID 66650300, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Add tert-butyl 4-(4-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (540 mg, 1.36 mmol) to diethyl ether (100 mL) and cool to 0° C. Add sodium hydride (55 mg, 1.5 mmol, 60% in mineral oil) to the mixture followed by methyl iodide (0.142 mL, 2.72 mmol). Stir the mixture for 1 h at 0° C. and warm to room temperature. Add THF (40 mL) and stir the mixture for 12 h. Concentrate the mixture, and purify the residue by silica gel chromatography (120 g RediSep column, elute with a gradient of 0% to 100% ethyl acetate:hexane, over 40 min, 85 mL/min) to provide tert-butyl 4-(1-methyl-4-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (425 mg, 76%).

Workup

  1. temperaturewarm to room temperature
  2. concentrationConcentrate the mixture
  3. custompurify the residue by silica gel chromatography (120 g RediSep column
  4. washelute with a gradient of 0% to 100% ethyl acetate
  5. waithexane, over 40 min

Sources & evidence

ORD record
ord-42f0cbc4f027405ba1aaa4a281752dd2
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

Loading…