HCID 86686305, compound → HCID 66613332, compound

HRID 406603Notes

Reaction equation

HRID 406603 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:13]([CH3:14])[N:12]=[C:11]([O:15][CH3:16])[C:10]=1[CH:17]=[O:18].[F:19][C:20]1[CH:25]=[CH:24][C:23]([Mg]Br)=[C:22]([CH3:28])[CH:21]=1>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:13]([CH3:14])[N:12]=[C:11]([O:15][CH3:16])[C:10]=1[CH:17]([C:23]1[CH:24]=[CH:25][C:20]([F:19])=[CH:21][C:22]=1[CH3:28])[OH:18]

Participants

4

Reactant 2

HCID 86686305HCID 86686305, compound2×HCID 178427853HCID 178427853, compound

Product 1

HCID 66613332HCID 66613332, compoundYield 83.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 5-(2,6-difluorophenyl)-3-methoxy-1-methyl-1H-pyrazole-4-carboxaldehyde (0.25 g, 0.99 mmol) (i.e. the product of Step D) in tetrahydrofuran (5 mL) at −30° C. was added 4-fluoro-2-methylphenylmagnesium bromide (0.5 M in hexanes, 2.0 mL, 1.0 mmol). The reaction mixture was allowed to warm to 0° C., quenched with saturated ammonium chloride solution and concentrated under reduced pressure. The resulting material was diluted with dichloromethane and water, poured onto a solid phase extraction tube (Varian Chem Elute®, prepacked with diatomaceous earth) and eluted with dichloromethane. The dichloromethane eluant was concentrated under reduced pressure and the resulting material purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in dichloromethane as eluant) to provide the title compound (0.3 g).

Workup

  1. customquenched with saturated ammonium chloride solution
  2. concentrationconcentrated under reduced pressure
  3. additionThe resulting material was diluted with dichloromethane and water
  4. additionpoured onto a solid phase extraction tube (Varian Chem Elute®, prepacked with diatomaceous earth)
  5. washeluted with dichloromethane
  6. concentrationThe dichloromethane eluant was concentrated under reduced pressure
  7. customthe resulting material purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in dichloromethane as eluant)

Sources & evidence

ORD record
ord-70ef4638afad431aa8b7ee88a52abf52
Source dataset
uspto-grants-2014_06
Patent number
US08754115B2

Reaction notes

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