Dimethylformamide → HCID 178496177, compound

HRID 1661965Notes

Reaction equation

HRID 1661965 reaction equation
[CH3:1][O:2][CH:3]([O:20][CH3:21])[CH2:4][O:5][C:6]1[C:7]([CH3:19])=[C:8]([CH:12]=[CH:13][C:14]=1[S:15]([CH3:18])(=[O:17])=[O:16])[C:9]([OH:11])=O.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[OH:33][C:34]1[N:38]([CH3:39])[N:37]=[CH:36][CH:35]=1>C(Cl)(Cl)Cl.C(OCC)(=O)C.C(N(CC)CC)C>[CH3:21][O:20][CH:3]([O:2][CH3:1])[CH2:4][O:5][C:6]1[C:7]([CH3:19])=[C:8]([C:9]([C:35]2[CH:36]=[N:37][N:38]([CH3:39])[C:34]=2[OH:33])=[O:11])[CH:12]=[CH:13][C:14]=1[S:15]([CH3:18])(=[O:17])=[O:16]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 67004126HCID 67004126, compoundHCID 178481816HCID 178481816, compound

Product 1

HCID 178496177HCID 178496177, compound

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(2,2-Dimethoxyethoxy)-2-methyl-4-(methylsulfonyl)benzoic acid (390 mg, 1.23 mmol) was dissolved in chloroform (15 mL), and oxalyl chloride (0.5 mL) and DMF in a catalytic amount were added thereto. The reaction mixture was stirred at room temperature for 30 minutes, and the solvent was distilled off under reduced pressure. The residue was dissolved in anhydrous THF (20 mL), and 5-hydroxy-1-methylpyrazole (132 mg, 1.35 mmol), triethylamine (250 mg) and N,N-dimethylaminopyridine (300 mg) were added, followed by reflux with heating for 1 hour. The reaction mixture was allowed to cool to room temperature, and ethyl acetate (200 mL) was added. The mixture was washed twice with a saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was dissolved in anhydrous acetonitrile (10 mL), and triethylamine (250 mg) and acetone cyanohydrin in a catalytic amount were added, followed by stirring for 12 hours at room temperature. The solvent was distilled off under reduced pressure to obtain crude 5-hydroxy-1-methylpyrazol-4-yl 3-(2,2-dimethoxyethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone.

Workup

  1. distillationthe solvent was distilled off under reduced pressure
  2. dissolutionThe residue was dissolved in anhydrous THF (20 mL)
  3. temperatureby reflux
  4. temperaturewith heating for 1 hour
  5. temperatureto cool to room temperature
  6. washThe mixture was washed twice with a saturated brine
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. dissolutionThe residue was dissolved in anhydrous acetonitrile (10 mL)
  10. additiontriethylamine (250 mg) and acetone cyanohydrin in a catalytic amount were added
  11. stirringby stirring for 12 hours at room temperature
  12. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-42fc947072dd4a77a3df931f6c116d17
Source dataset
uspto-grants-2011_10
Patent number
US08030498B2

Reaction notes

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