Isopropanol → tert-Butyl 4-(4-bromo-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2088883Notes

Reaction equation

HRID 2088883 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[N:5]([CH2:8][CH2:9][O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[C:6]=1Br.C([Li])CCC.C(O)(C)C>O1CCCC1.[Cl-].[NH4+]>[Br:1][C:2]1[N:3]=[C:4]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[N:5]([CH2:8][CH2:9][O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:6]=1

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 67264857tert-butyl 4-(4,5-dibromo-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 67265112tert-Butyl 4-(4-bromo-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylateYield 109.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-78 °C

Procedure

Add tert-butyl 4-(4,5-dibromo-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (46.00 g 85.61 mmol) in tetrahydrofuran (1 L). Cool to −78° C. under nitrogen. Add 1.6 M butyllithium in hexanes (90.97 mL, 1.7 eq) dropwise over 15 minutes. Maintain the internal temperature below −65° C. After 65 minutes, add isopropyl alcohol (50 mL). Allow to warm to room temperature over 2 hr. Dilute with saturated aqueous ammonium chloride, then extract with ethyl acetate three times. Wash the organics with saturated aqueous sodium chloride. Dry over anhydrous magnesium sulfate, filter, and concentrate in vacuo to give the title compound (43.00 g, 100%). MS (ES) m/z=460 [M]+.

Workup

  1. temperatureMaintain the internal temperature below −65° C
  2. temperatureAllow to warm to room temperature over 2 hr
  3. extractionextract with ethyl acetate three times
  4. washWash the organics with saturated aqueous sodium chloride
  5. dry with materialDry over anhydrous magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-0f6ff001b0c342f7a62cd69af8d80f81
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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