Methanol → 1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-formyl-4-pyridone

HRID 495525Notes

Reaction equation

HRID 495525 reaction equation
CC(C[AlH]CC(C)C)C.[F:10][C:11]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:12]=1[CH2:13][N:14]1[C:19]([CH3:20])=[C:18]([C:21](OCC)=[O:22])[C:17](=[O:26])[C:16]([Br:27])=[C:15]1[CH3:28].CO>C1COCC1.C(Cl)Cl>[F:10][C:11]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:12]=1[CH2:13][N:14]1[C:19]([CH3:20])=[C:18]([CH:21]=[O:22])[C:17](=[O:26])[C:16]([Br:27])=[C:15]1[CH3:28]

Participants

5

Reactant 3

HCID 887MethanolHCID 14487Diisobutylaluminum hydride2×HCID 223272271-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-ethoxycarbonyl-4-pyridone

Product 1

HCID 223272251-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-formyl-4-pyridoneYield 64.3%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

DIBAL (5.3 mmol, 5.3 mL of a 1.0 M solution in hexanes) was added dropwise via syringe to a stirred solution of 1-(2,6-difluorobenzyl)-2,6-dimethyl-3-bromo-5-ethoxycarbonyl-4-pyridone (1.40 g, 3.5 mmol) in THF/DCM (60 mL/20 mL), at −78° C. under N2. A suspension was formed at the end of the addition. After 1 hour, an additional aliquot of DIBAL (3.0 mmol, 3.0 mL of a 1.0 M solution in hexanes) was added. The reaction was deemed complete after 1 hour at −78° C. MeOH (5 mL) was carefully added to quench any unreacted DIBAL and the mixture was partitioned between EtOAc and 1 M HCl. The organic layer was separated and washed with brine, dried over anhydrous MgSO4 and filtered. Upon removal of the solvents in vacuum, the crude solid residue was triturated with Et2O. The product was obtained as a beige solid (0.80 g, 2.25 mmol, 64%). 1H NMR (CDCl3, 300 MHz): 10.55 (s, 1H), 7.40-7.33 (m, 1H), 7.00-6.93 (m, 2H), 5.38 (s, 2H), 2.78 (s, 3H), 2.69 (s, 3H); LRMS m/z 356.0 (M+−1), 358.0 (M++1).

Workup

  1. customA suspension was formed at the end of the addition
  2. waitThe reaction was deemed complete after 1 hour at −78° C
  3. customto quench any unreacted DIBAL
  4. customthe mixture was partitioned between EtOAc and 1 M HCl
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. customUpon removal of the solvents in vacuum
  10. customthe crude solid residue was triturated with Et2O

Sources & evidence

ORD record
ord-31ede86a44a544e69e8a42ec4ff5a872
Source dataset
uspto-grants-2005_09
Patent number
US06939883B2

Reaction notes

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