Dimethyl Sulfate → 4-(1-methyl-1H-pyrazol-3-yl)pyridine

HRID 1726393Notes

Reaction equation

HRID 1726393 reaction equation
O1CCC[CH2:2]1.[NH:6]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[N:7]1.[H-].[Na+].COS(OC)(=O)=O>CCCCCC.C(OCC)C>[CH3:2][N:6]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[N:7]1

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 178419957HCID 178419957, compound

Product 1

HCID 200610284-(1-methyl-1H-pyrazol-3-yl)pyridineYield 55%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Procedure

To 150 mL tetrahydrofuran was added 4-(1H-pyrazol-3-yl)pyridine (4.96 g; Example 3, Step 1) and the solution cooled in ice. To this was added slowly 1.64 g of a 60% suspension of sodium hydride in mineral oil. After gas evolution ceased, the mixture was stirred at ambient temperature for 30 min, cooled back down in ice, and 3.4 mL dimethylsulfate was added. The mixture was allowed to slowly warm to ambient temperature. After 1 hour the reaction mixture was evaporated and the dark brown residue partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The ethyl acetate was washed with saturated aqueous sodium bicarbonate, brine, dried over magnesium sulfate, filtered, and evaporated under vacuum to afford 4.6 g crude product as a pale yellow solid. The crude material was taken up in a diethyl ether and hexane mixture, filtered through celite, and allowed to crystallize. A total of 2.98 g (55% yield) pale yellow crystals were obtained. 1H NMR (CDCl3) was consistent with a single isomer of the desired structure. LC/MS showed one peak with a M+1 molecular ion of m/z 160.5 by positive ESI.

Workup

  1. temperaturethe solution cooled in ice
  2. temperaturecooled back down in ice
  3. temperatureto slowly warm to ambient temperature
  4. customAfter 1 hour the reaction mixture was evaporated
  5. customthe dark brown residue partitioned between saturated aqueous sodium bicarbonate and ethyl acetate
  6. washThe ethyl acetate was washed with saturated aqueous sodium bicarbonate, brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated under vacuum
  10. customto afford 4.6 g crude product as a pale yellow solid
  11. filtrationfiltered through celite
  12. customto crystallize

Sources & evidence

ORD record
ord-cc2ab0ba375d44d1acf4d925d1fda67b
Source dataset
uspto-grants-2009_02
Patent number
US07491829B2

Reaction notes

Loading…