Sodium Iodide → Tert-butyl 4-[1-(2-pyrrolidin-1-ylethyl)-4-tetrahydropyran-4-yl-imidazol-2-yl]piperidine-1-carboxylate

HRID 2088913Notes

Reaction equation

HRID 2088913 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[N:8]=[C:9]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[NH:10][CH:11]=2)[CH2:3][CH2:2]1.[OH-].[K+].[I-].[Na+].[Cl-].Cl[CH2:31][CH2:32][NH+:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1>CS(C)=O>[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[N:8]=[C:9]([CH:12]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]3)[N:10]([CH2:31][CH2:32][N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:11]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 14797Potassium HydroxideHCID 110083397250-67-1HCID 178451797HCID 178451797, compound

Product 1

HCID 67112170Tert-butyl 4-[1-(2-pyrrolidin-1-ylethyl)-4-tetrahydropyran-4-yl-imidazol-2-yl]piperidine-1-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Combine tert-butyl 4-(4-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-2-yl)piperidine-1-carboxylate (101.10 g, 301.39 mmol) and freshly ground potassium hydroxide (50.73 g, 3.0 eq) in dimethyl sulfoxide (500 mL). Stir for 15 minutes, then add sodium iodide (49.69 g, 1.1 eq). Add a solution of 1-(2-chloro-ethyl)-pyrrolidinium chloride (66.64 g, 1.3 eq) in dimethyl sulfoxide (1.01 L) and stir for four hours at room temperature. Pour the contents of the reaction into an ice/water mixture (˜1 L) and extract with methyl tert-butyl ether. Dry the organics over anhydrous magnesium sulfate, filter, and concentrate in vacuo. Purify by HPLC (Chiralpak AD basic, hexane/ethanol 9:1) to give tert-butyl 4-(4-(tetrahydro-2H-pyran-4-yl)-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (82.0 g, 63%). MS (ES) m/z=433 [M]+.

Workup

  1. stirringstir for four hours at room temperature
  2. additionPour
  3. extractionextract with methyl tert-butyl ether
  4. dry with materialDry the organics over anhydrous magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by HPLC (Chiralpak AD basic, hexane/ethanol 9:1)

Sources & evidence

ORD record
ord-fa8e2333117142fab376dc33c29fcd72
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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