Tetrahydrofuran → ethyl 1-(3-chloro-2-pyridinyl)-3-isopropyl-1H-pyrazole-5-carboxylate

HRID 2427062Notes

Reaction equation

HRID 2427062 reaction equation
CON=[C:4]([CH2:10][C:11](=O)[CH:12]([CH3:14])[CH3:13])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[Cl:16][C:17]1[C:18]([NH:23][NH2:24])=[N:19][CH:20]=[CH:21][CH:22]=1.O1CCCC1>C(O)(=O)C>[Cl:16][C:17]1[C:18]([N:23]2[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:10][C:11]([CH:12]([CH3:13])[CH3:14])=[N:24]2)=[N:19][CH:20]=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 5561003-Chloro-2-hydrazinylpyridineHCID 86632548Ethyl 2-methoxyimino-5-methyl-4-oxohexanoate

Product 1

HCID 66855071ethyl 1-(3-chloro-2-pyridinyl)-3-isopropyl-1H-pyrazole-5-carboxylateYield 26.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 3.0 g of ethyl 2-methoxyimino-5-methyl-4-oxohexanoate, 2.4 g of 3-chloro-2-hydrazinopyridine, 50 ml of tetrahydrofuran and 100 ml of acetic acid was stirred at room temperature for 20 hours, and then heated to reflux for 4 hours. The reaction mixture was concentrated under reduced pressure. Water was poured into the residue, and the mixture was extracted with methyl t-butyl ether two times. The combined organic layer was washed successively with a 1N aqueous sodium hydroxide solution, water and an aqueous saturated chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 1.07 g of ethyl 1-(3-chloro-2-pyridinyl)-3-isopropyl-1H-pyrazole-5-carboxylate of the formula:

Workup

  1. temperatureheated
  2. temperatureto reflux for 4 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionWater was poured into the residue
  5. extractionthe mixture was extracted with methyl t-butyl ether two times
  6. washThe combined organic layer was washed successively with a 1N aqueous sodium hydroxide solution, water
  7. dry with materialan aqueous saturated chloride solution, dried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9c14606b775541a499a523b276ee3614
Source dataset
uspto-grants-2011_06
Patent number
US07968573B2

Reaction notes

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