Cesium carbonate → 1-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 1849000Notes

Reaction equation

HRID 1849000 reaction equation
[NH:1]1[CH:5]=[C:4]([B:6]2[O:14][C:11]([CH3:13])([CH3:12])[C:8]([CH3:10])([CH3:9])[O:7]2)[CH:3]=[N:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:22][CH2:23][O:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][O:26]1>CN(C=O)C>[O:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH:25]1[O:24][CH2:23][CH2:22][N:2]1[CH:3]=[C:4]([B:6]2[O:7][C:8]([CH3:9])([CH3:10])[C:11]([CH3:13])([CH3:12])[O:14]2)[CH:5]=[N:1]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-pyrazole boronic acid pinacol ester (2.0 g, 10.3 mmol) in anhydrous DMF (20 mL) was added cesium carbonate (4.03 g, 12.4 mmol) and the mixture stirred at RT for 10 minutes. 2-(2-Bromoethoxy)tetrahydro-2H-pyran (1.87 mL, 12.4 mmol) was added in two portions and the mixture was heated to 70° C. After heating for 18 hours the mixture was allowed to cool to RT and partitioned between water (100 mL) and EtOAc (100 mL). The aqueous layer was washed with EtOAc (3×20 mL) and the combined organic layers washed with water (3×100 mL) followed by brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, gradient 0-100% EtOAc in cyclohexane) to afford the title compound (2.15 g, 65%). LCMS: RT=3.97 min, [M+Na]+=345

Workup

  1. temperaturethe mixture was heated to 70° C
  2. temperatureAfter heating for 18 hours the mixture
  3. temperatureto cool to RT
  4. custompartitioned between water (100 mL) and EtOAc (100 mL)
  5. washThe aqueous layer was washed with EtOAc (3×20 mL)
  6. washthe combined organic layers washed with water (3×100 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resultant residue was purified by flash chromatography (SiO2, gradient 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-f7e61a67aa99473290462cc7ee29a1db
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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