Dimethyl Sulfoxide → 6-Methoxy-4-(trifluoromethyl)-3-pyridinecarboxaldehyde

HRID 2265963Notes

Reaction equation

HRID 2265963 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH3:11][O:12][C:13]1[N:18]=[CH:17][C:16]([CH2:19][OH:20])=[C:15]([C:21]([F:24])([F:23])[F:22])[CH:14]=1.C(N(CC)CC)C>ClCCl>[CH3:11][O:12][C:13]1[N:18]=[CH:17][C:16]([CH:19]=[O:20])=[C:15]([C:21]([F:24])([F:22])[F:23])[CH:14]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68785918HCID 68785918, compound

Product 1

HCID 866255266-Methoxy-4-(trifluoromethyl)-3-pyridinecarboxaldehydeYield 74.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a cooled (−78° C.) solution of DMSO (0.15 mL, 2.13 mmol) in dichloromethane (2 mL) was added oxalyl chloride (0.14 mL, 1.60 mmol), and the mixture was stirred for 10 minutes. 6-Methoxy-4-trifluoromethyl-3-pyridinemethanol (220 mg, 1.06 mmol) in dichloromethane (4 mL) was added to the reaction mixture. After stirring at −40° C. for 50 minutes, the mixture was treated with triethylamine (0.44 mL, 3.16 mmol), stirred for 90 minutes while warming to room temperature, and quenched with water. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give 6-methoxy-4-trifluoromethyl-3-pyridinecarboxaldehyde (162 mg, 74.4%) as a solid. The crude product was used directly in the following Swern oxidation.

Workup

  1. stirringAfter stirring at −40° C. for 50 minutes
  2. stirringstirred for 90 minutes
  3. customquenched with water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cff170eb96f1438e8ca4dff6cd9f23f0
Source dataset
uspto-grants-2010_12
Patent number
US07858621B2

Reaction notes

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