Sodium hydride → HCID 66740166, compound

HRID 1627318Notes

Reaction equation

HRID 1627318 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].Cl[CH2:18][C:19]1[N:20]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)[C:21]([C:24]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=2)([CH3:26])[CH3:25])=[CH:22][N:23]=1>C1COCC1>[Cl:34][C:29]1[CH:28]=[C:27]([C:24]([C:21]2[N:20]([C:35]3[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=3)[C:19]([CH2:18][O:1][CH:2]3[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]3)=[N:23][CH:22]=2)([CH3:26])[CH3:25])[CH:32]=[CH:31][C:30]=1[Cl:33]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 667400042-(chloromethyl)-5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

Product 1

HCID 66740166HCID 66740166, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (202 mg, 1 mmol) in anhyd THF (3 mL) was added NaH (60% in mineral oil, 53 mg, 1.32 mmol). The mixture stirred at room temperature for 30 min, then a solution of 2-(chloromethyl)-5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (262 mg, 0.66 mmol) in THF (2 mL) was added. After stirring at ambient temperature overnight, the reaction was quenched by addition of MeOH and concentrated in vacuo. The residue was partitioned in water and EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, concentrated in vacuo, and purified by column chromatography (silica, 0-90% EtOAc/Hex) to give tert-butyl 4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)methoxy)piperidine-1-carboxylate as a white solid (215 mg, 60%).

Workup

  1. stirringAfter stirring at ambient temperature overnight
  2. customthe reaction was quenched by addition of MeOH
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned in water
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography (silica, 0-90% EtOAc/Hex)

Sources & evidence

ORD record
ord-7348cfd03871494d8cb805fda35816d3
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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