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

HRID 2088888Notes

Reaction equation

HRID 2088888 reaction equation
Br[C:2]1[N:3]=[C:4]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[N:5]([CH2:7][CH2:8][OH:9])[CH:6]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:31]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCC[CH2:32]1.CC1(C)C(C)(C)OB(C=C)O1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:31]([C:2]1[N:3]=[C:4]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[N:5]([CH2:7][CH2:8][OH:9])[CH:6]=1)=[CH2:32]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 67265139tert-Butyl 4-(4-bromo-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

Product 1

HCID 67112049tert-Butyl 4-(4-vinyl-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylateYield 454.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Add tert-butyl 4-(4-bromo-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (42.00 g, 112.22 mmol) in 1,4-dioxane (400 mL) and water (200 mL). Add potassium phosphate, tribasic, N-hydrate (47.64 g, 2.0 eq) and dicyclohexyl-[2-(2,6-dimethoxyphenyl)phenyl]phosphane (5.76 g, 0.12 eq). Degas with nitrogen for 5 minutes. Add 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (30.25 mL, 1.5 eq) then degas for another 10 minutes. Add palladium acetate (1.26 g, 0.05 eq) and reflux at 120° C. overnight. Stop heating after 12 hrs. Filter through Celite®. Wash with dichloromethane and methanol. Concentrate to dryness in vacuo. Dilute with saturated aqueous sodium chloride then extract with ethyl acetate three times. Dry over anhydrous sodium sulfate and concentrate in vacuo. Purify by silica gel chromatography, eluting with 50-90% ethyl acetate/hexanes, to give the title compound as a yellow foam (20.50 g, 56%). MS (ES) m/z=322 [M]+.

Workup

  1. customDegas with nitrogen for 5 minutes
  2. temperatureStop heating after 12 hrs
  3. filtrationFilter through Celite®
  4. washWash with dichloromethane and methanol
  5. concentrationConcentrate to dryness in vacuo
  6. additionDilute with saturated aqueous sodium chloride
  7. extractionthen extract with ethyl acetate three times
  8. dry with materialDry over anhydrous sodium sulfate
  9. concentrationconcentrate in vacuo
  10. customPurify by silica gel chromatography
  11. washeluting with 50-90% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-5ea2b63548734fc1a57766c25ccb8381
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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