Formaldehyde → HCID 114844633, compound

HRID 1499112Notes

Reaction equation

HRID 1499112 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[N:9]1[CH:13]=[CH:12][C:11]([CH3:14])=[N:10]1.BrC1C=CC(Cl)=CC=1N1C(C)=CC=N1.C([Mg]Cl)(C)C.C=O.CN([CH:39]=[O:40])C>C1COCC1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([CH:39]=[O:40])=[C:3]([N:9]2[CH:13]=[CH:12][C:11]([CH3:14])=[N:10]2)[CH:4]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6228DimethylformamideHCID 131734237HCID 131734237, compound2×HCID 178418918HCID 178418918, compound

Product 1

HCID 114844633HCID 114844633, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(2-bromo-5-chlorophenyl)-3-methyl-1H-pyrazole/1-(2-bromo-5-chlorophenyl)-5-methyl-1H-pyrazole mixture (Intermediate 3, step 1) (1.00 g, 3.68 mmol) was dissolved in THF (6 mL) then cooled to 0° C. i-Propyl magnesium chloride (2.76 mL, 2.0 M in THF, 5.52 mmol) was added dropwise and the reaction was warmed to RT for 30 min. The reaction was then cooled to −15° C. and paraformaldehyde (166 mg, 5.5 mmol) was added. The reaction mixture was allowed to warm to RT and stirred for 1 h. DMF (500 mL) was added and the reaction was stirred for an additional 1 h. The reaction was quenched with HCl (2 N, 4 mL), diluted with water, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column chromatography (EtOAc/heptane) provided 4-chloro-2-(3-methyl-pyrazol-1-yl)-benzaldehyde.

Workup

  1. additionwas added dropwise
  2. temperatureThe reaction was then cooled to −15° C.
  3. temperatureto warm to RT
  4. stirringthe reaction was stirred for an additional 1 h
  5. customThe reaction was quenched with HCl (2 N, 4 mL)
  6. additiondiluted with water
  7. extractionextracted with EtOAc
  8. washwashed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification by normal phase silica gel column chromatography (EtOAc/heptane)

Sources & evidence

ORD record
ord-e33875f7ac1445a59541f70e3d5f5139
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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