Diisobutylaluminum hydride → 4-(4-Fluorophenyl)-2-pyrimidinecarboxaldehyde

HRID 1472883Notes

Reaction equation

HRID 1472883 reaction equation
CC(C[AlH]CC(C)C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([C:23](OC)=[O:24])[N:18]=2)=[CH:13][CH:12]=1>C1(C)C=CC=CC=1>[F:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([CH:23]=[O:24])[N:18]=2)=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydride3×HCID 68312492HCID 68312492, compound

Product 1

HCID 839161854-(4-Fluorophenyl)-2-pyrimidinecarboxaldehydeYield 10.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

DIBAL-H (3.62 mL, 3.62 mmol, 1.0 M in toluene) was slowly added to a suspension of Example 32A (700 mg, 3.01 mmol) in toluene (30 mL) at −75° C. After 2 hours, DIBAL-H (1.507 mL, 1.507 mmol, 1.0 M in toluene) was added to the reaction mixture and warmed slowly to ambient temperature overnight. The reaction was a clear orange-red solution and the methyl ester was consumed, yielding a mixture of aldehyde and alcohol. Additional DIBAL-H (1.507 mL, 1.507 mmol, 1.0 M in toluene) was added at ambient temperature. After 4 hours, the reaction was quenched with 5% acetic acid in water (200 mL), extracted twice with EtOAc (200 mL), washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on a Grace Reveleris 12 g column, eluted with 0-60% EtOAc in dichloromethane (25 mL/min) to provide the title compound (62 mg, 0.307 mmol, 10.17% yield) as an off-white solid. MS (ESI+) m/z 234.8 (M+H-MeOH); 1H NMR (300 MHz, DMSO-d6) δ 10.04 (s, 1H), 9.12 (d, J=5.3, 1H), 8.38 (dd, J=9.0, 5.5, 2H), 8.32 (d, J=5.4, 1H), 7.45 (t, J=8.9, 2H).

Workup

  1. customthe methyl ester was consumed
  2. customyielding
  3. waitAfter 4 hours
  4. customthe reaction was quenched with 5% acetic acid in water (200 mL)
  5. extractionextracted twice with EtOAc (200 mL)
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was chromatographed on a Grace Reveleris 12 g column
  11. washeluted with 0-60% EtOAc in dichloromethane (25 mL/min)

Sources & evidence

ORD record
ord-8ad140db92de4388a8993e556d5f7ce6
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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