Dimethyl Sulfoxide → 4-(5-Ethoxy-2-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carbaldehyde

HRID 2207667Notes

Reaction equation

HRID 2207667 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:13][C:14]1[CH:15]=[CH:16][C:17]([F:30])=[C:18]([C:20]2[CH:25]=[C:24]([CH3:26])[N:23]=[C:22]([CH2:27][OH:28])[C:21]=2[CH3:29])[CH:19]=1)[CH3:12].C(N(CC)CC)C>C(Cl)Cl>[CH2:11]([O:13][C:14]1[CH:15]=[CH:16][C:17]([F:30])=[C:18]([C:20]2[CH:25]=[C:24]([CH3:26])[N:23]=[C:22]([CH:27]=[O:28])[C:21]=2[CH3:29])[CH:19]=1)[CH3:12]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 89648949[4-(5-Ethoxy-2-fluoro-phenyl)-3,6-dimethyl-2-pyridyl]methanol

Product 1

HCID 896490794-(5-Ethoxy-2-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carbaldehydeYield 67.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of oxalyl chloride (1.46 mL, 17.3 mmol) in DCM (50 mL) cooled to −78° C. was added dropwise, a solution of dimethyl sulfoxide (2.68 mL, 37.74 mmol) in DCM (5 mL). After addition, the solution was stirred for 15 mins. A solution of [4-(5-ethoxy-2-fluoro-phenyl)-3,6-dimethyl-2-pyridyl]methanol (which may be prepared as described in Description 140) (4.33 g, 15.73 mmol) in DCM (10 mL) was then added dropwise over about 5 mins. The mixture was allowed to stir at −78° C. for 2 hrs. Triethylamine (8.74 mL, 62.91 mmol) was added dropwise giving a precipitate and this was allowed to warm to room temperature over one hour. The reaction mixture was washed with water and brine, dried over magnesium sulphate and evaporated. The crude residue was purified by silica gel chromatography (50 g SiO2) eluting with ethyl acetate in iso-hexane (0-40%). Evaporation of desired fractions gave 4-(5-ethoxy-2-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carbaldehyde (D141) (2.89 g, 10.574 mmol, 67.2% yield) as a yellow solid;

Workup

  1. additionwas added dropwise
  2. additionAfter addition
  3. stirringto stir at −78° C. for 2 hrs
  4. customgiving a precipitate
  5. washThe reaction mixture was washed with water and brine
  6. dry with materialdried over magnesium sulphate
  7. customevaporated
  8. customThe crude residue was purified by silica gel chromatography (50 g SiO2)
  9. washeluting with ethyl acetate in iso-hexane (0-40%)
  10. customEvaporation of desired fractions

Sources & evidence

ORD record
ord-e3b1bf61706541189faab1076ff84df0
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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