Potassium Carbonate → 5-Bromo-3-fluoro-2-(2-pyrazol-1-yl-ethoxy)-pyridine

HRID 873325Notes

Reaction equation

HRID 873325 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([F:9])[C:5]([OH:8])=[N:6][CH:7]=1.Cl[CH2:11][CH2:12][N:13]1[CH:17]=[CH:16][CH:15]=[N:14]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([F:9])[C:5]([O:8][CH2:11][CH2:12][N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 6422141-(2-Chloroethyl)-1H-pyrazoleHCID 1785175945-Bromo-3-fluoro-1,2-dihydropyridin-2-one

Product 1

HCID 709790075-Bromo-3-fluoro-2-(2-pyrazol-1-yl-ethoxy)-pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A vigorously stirred mixture of 5-bromo-3-fluoro-2-hydroxypyridine (440 mg, 2.3 mmol), 1-(2-chloroethyl)-1H-pyrazole (330 mg, 2.5 mmol) and K2CO3 (380 mg, 2.77 mmol) in DMF (5 mL) was heated to 90° C. for 16 h. After cooling to room temperature the solvent was removed in vacuo and the crude partitioned between water and EtOAc. The aqueous was extracted with EtOAc (×3) and the combined organics dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (gradient: 20%-100% EtOAc in pet. ether 40-60) yielded 5-bromo-3-fluoro-2-(2-pyrazol-1-yl-ethoxy)-pyridine as a clear oil.

Workup

  1. temperatureAfter cooling to room temperature the solvent
  2. customwas removed in vacuo
  3. customthe crude partitioned between water and EtOAc
  4. extractionThe aqueous was extracted with EtOAc (×3)
  5. dry with materialthe combined organics dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by column chromatography (gradient: 20%-100% EtOAc in pet. ether 40-60)

Sources & evidence

ORD record
ord-89818f11e18c4b63bd6802baf424dbdb
Source dataset
uspto-grants-2015_03
Patent number
US08975406B2

Reaction notes

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