Sodium hydride → HCID 19436795, compound

HRID 1735001Notes

Reaction equation

HRID 1735001 reaction equation
[CH3:1][N:2]1[C:6]([O:7][C:8]2[N:13]=[N:12][CH:11]=[C:10]([OH:14])[CH:9]=2)=[CH:5][C:4]([C:15]([F:18])([F:17])[F:16])=[N:3]1.[H-].[Na+].C(OC1C=C(OC2N(C)N=C([C:37](F)([F:39])[F:38])C=2)N=NC=1)C>CN(C=O)C>[F:38][CH:37]([F:39])[O:14][C:10]1[CH:9]=[C:8]([O:7][C:6]2[N:2]([CH3:1])[N:3]=[C:4]([C:15]([F:18])([F:16])[F:17])[CH:5]=2)[N:13]=[N:12][CH:11]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 19436778HCID 19436778, compoundHCID 178481860HCID 178481860, compound

Product 1

HCID 19436795HCID 19436795, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

6-[[1-Methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]oxy]-4-pyridazinol (Compound No. 12, 1.0 g, 0.0038 mole) and NaH (1.15 g of 80% NaH in oil, 0.0384 mole) were heated to 80° C. in DMF (20 mL) while CF2ClH was continuously bubbled through the solution for 6.5 h. The mixture was cooled to 0° C. and quenched by dropwise addition of water under an N2 sweep. After H2 ceased to evolve the mixture was poured into water/ethyl acetate and made acidic with excess ammonium chloride and then extracted 3×100 mL with ethyl acetate. The organic layers were extracted with brine, dried (MgSO4), filtered through silica gel with ethyl acetate, and evaporated in vacuo. Two compounds were present as evidenced by TLC. The mixture was separated by reverse phase chroma-tography to give 5-(difluoromethoxy)-3-[[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]oxy]pyridazine (0.144 g, 12% yield) as a yellow solid (mp= 86 -88° C.) and 5-ethoxy-3-[[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]oxy]pyridazine (0.058 g, 5% yield as a yellow solid.

Workup

  1. customwas continuously bubbled through the solution for 6.5 h
  2. customquenched by dropwise addition of water under an N2 sweep
  3. additionwas poured into water/ethyl acetate
  4. extractionextracted 3×100 mL with ethyl acetate
  5. extractionThe organic layers were extracted with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered through silica gel with ethyl acetate
  8. customevaporated in vacuo
  9. customThe mixture was separated by reverse phase chroma-tography

Sources & evidence

ORD record
ord-9b1c996395294a12804d5b2bbcc9a2b3
Source dataset
uspto-grants-1996_07
Patent number
US05536701

Reaction notes

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