Diethyl Ether → 2-(1H-Pyrazol-3-Yl)Pyridine

HRID 1532567

Reaction equation

HRID 1532567 reaction equation
Cl[C:2]1[C:3]([C:9]2[CH:13]=[C:12](C(F)(F)F)[NH:11][N:10]=2)=[N:4][CH:5]=[C:6](Cl)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].CI.C(OCC)C>CN1CCCC1=O.O>[N:4]1[CH:5]=[CH:6][CH:7]=[CH:2][C:3]=1[C:9]1[NH:10][N:11]=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 21712162HCID 21712162, compound

Product 1

HCID 27976572-(1H-Pyrazol-3-Yl)PyridineYield 86.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
55 °C

Procedure

8.88 g of 3-(3,5-dichloro-2-pyridyl)-5-trifluoromethyl-[1H]-pyrazole (Example H11) are initially introduced into 35 ml of N-methylpyrrolidone. After addition of 13.0 g of potassium carbonate, the mixture is stirred and heated up to 55° C. 2.36 ml of methyl iodide in 5.0 ml of N-methylpyrrolidone are then slowly added dropwise. After the mixture has been subsequently stirred for 2 hours, diethyl ether and water are added, the mixture is extracted by shaking and the organic phase is separated off. The ether phase which has been separated off is washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product is purified by means of flash chromatography (silica gel; eluting agent: toluene/ethyl acetate 100/1). First, 3.96 g of the isomeric 5-pyridylpyrazole (yield 42%) are isolated as a yellow oil, and then 1.96 g of the 3-pyridylpyrazoie (yield 21%) are isolated as a yellow solid. The Rf values of the two isomeric 3- and 5-pyridyipyrazoles are as follows on silica gel 60 F254 with toluenelethyl acetate 30/1 as the eluting agent (UV):

Workup

  1. stirringAfter the mixture has been subsequently stirred for 2 hours
  2. extractionthe mixture is extracted
  3. stirringby shaking
  4. customthe organic phase is separated off
  5. customThe ether phase which has been separated off
  6. washis washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product is purified by means of flash chromatography (silica gel; eluting agent: toluene/ethyl acetate 100/1)

Sources & evidence

ORD record
ord-69a9b53d7d414033b6c8974eb2ef21d4
Source dataset
uspto-grants-2001_03
Patent number
US06204221B1

Linked notes

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