Potassium Phosphate, Tribasic → tert-Butyl 4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-vinyl-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2088895Notes

Reaction equation

HRID 2088895 reaction equation
Br[C:2]1[N:3]=[C:4]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[N:5]([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:6]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:35]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCC[CH2:36]1.CC1(C)C(C)(C)OB(C=C)O1>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[N:9]1([CH2:8][CH2:7][N:5]2[CH:6]=[C:2]([CH:35]=[CH2:36])[N:3]=[C:4]2[CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 67112012tert-Butyl 4-(4-bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

Product 1

HCID 67968742tert-Butyl 4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-vinyl-1H-imidazol-2-yl)piperidine-1-carboxylateYield 426.3%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Add tert-butyl 4-(4-bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (0.26 g, 0.60 mmol) in 1,4-dioxane (4 mL) and water (1 mL). Add potassium phosphate, tribasic, N-hydrate (0.26 g, 2.0 eq) and dicyclohexyl-[2-(2,6-dimethoxyphenyl)phenyl]phosphane (0.036 g, 0.15 eq). Add 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.22 mL, 2.05 eq) and degas for 10 minutes. Add bis(dibenzylideneacetone)palladium(0) (0.03 g, 0.06 eq) and reflux at 150° C. for 1 hour. Filter through Celite®. Wash with dichloromethane. Concentrate the filtrate to dryness in vacuo. Purify by silica gel chromatography, eluting with 25% methanol/ethyl acetate, to give the title compound as a yellow foam (0.14 g, 38%). MS (ES) m/z=375 [M]+.

Workup

  1. filtrationFilter through Celite®
  2. washWash with dichloromethane
  3. concentrationConcentrate the filtrate to dryness in vacuo
  4. customPurify by silica gel chromatography
  5. washeluting with 25% methanol/ethyl acetate

Sources & evidence

ORD record
ord-850bf39ada92498aa64d22e96d5b3d2e
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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