Tetrahydrofuran → methyl 1-(3,5-dichloropyridin-2-yl)-3-methyl-1H-pyrazole-5-carboxylate

HRID 453067

Reaction equation

HRID 453067 reaction equation
O=[C:2]([CH2:7][C:8](=O)[CH3:9])[C:3]([O:5][CH3:6])=[O:4].O1CCCC1.[Cl:16][C:17]1[C:18]([NH:24][NH2:25])=[N:19][CH:20]=[C:21]([Cl:23])[CH:22]=1>C(O)(=O)C>[Cl:16][C:17]1[C:18]([N:24]2[C:2]([C:3]([O:5][CH3:6])=[O:4])=[CH:7][C:8]([CH3:9])=[N:25]2)=[N:19][CH:20]=[C:21]([Cl:23])[CH:22]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 88600Methyl acetopyruvateHCID 6009663,5-Dichloro-2-hydrazinylpyridine

Product 1

HCID 58158937methyl 1-(3,5-dichloropyridin-2-yl)-3-methyl-1H-pyrazole-5-carboxylateYield 50.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a 100 mL flask, methyl 2,4-dioxopentanoate (2.88 g, 0.020 mol), tetrahydrofuran (15 mL), acetic acid (30 mL), and 3,5-dichloro-2-hydrazinylpyridine (3.56 g, 0.020 mol) were added sequentially. The reaction mixture was heated to reflux for 2 hours and then the mixture was concentrated by rotary evaporator. Then ethyl acetate (150 mL) and water (100 mL) was added, the organic layer was washed with saturated sodium bicarbonate solution (100 mL) and saturated brine (100 mL), dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by silica gel column chromatography (Fluent: ethyl acetate/petroleum ether=1/5) to give the product (2.9 g) as a white solid in 50% yield. Melting point: 97-98° C. 1H NMR (300 MHz, CDCl3): 8.432 (d, 1H), 7.888 (d, 1H), 6.802 (s, 1H), 3.760 (s, 3H), 2.370 (s, 3H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. concentrationthe mixture was concentrated by rotary evaporator
  4. additionThen ethyl acetate (150 mL) and water (100 mL) was added
  5. washthe organic layer was washed with saturated sodium bicarbonate solution (100 mL) and saturated brine (100 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated by rotary evaporator
  8. customThe residue was purified by silica gel column chromatography (Fluent: ethyl acetate/petroleum ether=1/5)

Sources & evidence

ORD record
ord-e9c01f6cde2f4ce9a71528648443ae37
Source dataset
uspto-grants-2013_07
Patent number
US08492409B2

Linked notes

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