Hydrochloric Acid → 2-Fluoro-4-(1H-pyrazol-1-yl)benzaldehyde

HRID 1166085Notes

Reaction equation

HRID 1166085 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[F:11][C:12]1[CH:19]=[C:18]([N:20]2[CH:24]=[CH:23][CH:22]=[N:21]2)[CH:17]=[CH:16][C:13]=1[C:14]#N.C[OH:26].Cl>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:11][C:12]1[CH:19]=[C:18]([N:20]2[CH:24]=[CH:23][CH:22]=[N:21]2)[CH:17]=[CH:16][C:13]=1[CH:14]=[O:26]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 21225700DiisobutylaluminumhydrideHCID 226311842-Fluoro-4-(1H-pyrazol-1-yl)benzonitrile

Product 1

HCID 226310262-Fluoro-4-(1H-pyrazol-1-yl)benzaldehydeYield 65%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diisobutylaluminum hydride (1.0 M in toluene, 11.00 mL, 11.00 mol) was added dropwise over 10 min to a vigorously stirred suspension of the compound from step A (1.88 g, 10.04 mmol) in toluene (100 mL) at −78° C. After 1 h at −78° C., MeOH (1 mL) was added, the mixture was stirred for 5 min, and then poured into a stirred, cold (0° C.) mixture of 1.2 N HCl (100 mL) and ethyl acetate (100 mL). After stirring for 30 min at RT, the layers were separated and the aqueous layer was extracted with additional ethyl acetate (100 mL). The combined organic layers were washed with sat. aq. NaHCO3 (100 mL) and brine (100 mL), dried (MgSO4), and concentrated. Recrystallization from IPA followed by chromatography (SiO2, dichloromethane) provided 1.25 g (65%) of the title compound as a colorless solid. MS 191 (M+H)+.

Workup

  1. stirringAfter stirring for 30 min at RT
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with additional ethyl acetate (100 mL)
  4. washThe combined organic layers were washed with sat. aq. NaHCO3 (100 mL) and brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customRecrystallization from IPA

Sources & evidence

ORD record
ord-3781f59248a140a1852d05f2f9099c27
Source dataset
uspto-grants-2003_09
Patent number
US06613747B2

Reaction notes

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