Citric Acid → HCID 67342382, compound

HRID 1672294Notes

Reaction equation

HRID 1672294 reaction equation
C(Cl)(=O)C(Cl)=O.[NH2:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11]([Br:15])=[CH:10][N:9]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].O1CCCC1.[Br:31][C:32]1[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][C:33]=1[O:34][C:35]([CH3:40])([CH3:39])[C:36](Cl)=[O:37].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(=O)([O-])O.[Na+]>ClCCl.O1CCCC1.C(=O)=O.CC(C)=O.CN(C)C=O>[Br:15][C:11]1[CH:12]=[C:13]([CH3:14])[C:8]([NH:7][C:36](=[O:37])[C:35]([O:34][C:33]2[CH:41]=[C:42]([N+:45]([O-:47])=[O:46])[CH:43]=[CH:44][C:32]=2[Br:31])([CH3:40])[CH3:39])=[N:9][CH:10]=1

Participants

11

Reactant 6

HCID 311Citric AcidHCID 65578Oxalyl chlorideHCID 1379342-Amino-5-bromo-3-methylpyridineHCID 516892Sodium BicarbonateHCID 23714775LiHMDS tetrahydrofuranHCID 86626314HCID 86626314, compound

Product 1

HCID 67342382HCID 67342382, compound

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 18522661Acetone cardiceSolvent

Procedure

To a solution of the compound obtained in Reference Example 63(1) (295 mg) in dichloromethane (10 mL) were added oxalyl chloride (253 μL) and a drop of N,N-dimethylformamide, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to give crude 2-(2-bromo-5-nitrophenoxy)-2-methylpropionyl chloride. To a solution of 2-amino-5-bromo-3-methylpyridine (727 mg) in tetrahydrofuran (20 mL) was added dropwise 1M lithium bis(trimethylsilyl)amide-tetrahydrofuran solution (3.88 mL) over a period of one minute under cooling in dry ice-acetone bath under argon atmosphere. The mixture was stirred at the same temperature for 5 minutes. Thereto was added quickly a solution of 2-(2-bromo-5-nitrophenoxy)-2-methylpropionyl chloride in tetrahydrofuran (10 mL), and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added an aqueous citric acid solution, and the mixture was basified with an aqueous saturated sodium hydrogencarbonate solution and extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on NH-silica gel (Chromatorex NH-silica gel; solvent; n-hexane/ethyl acetate=19/1→3/1) to give N-(5-bromo-3-methylpyridin-2-yl)-2-(2-bromo-5-nitrophenoxy)-2-methylpropionamide (599 mg) as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto give crude 2-(2-bromo-5-nitrophenoxy)-2-methylpropionyl chloride
  3. stirringthe mixture was stirred at the same temperature for 30 minutes
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed successively with water and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on NH-silica gel (Chromatorex NH-silica gel; solvent; n-hexane/ethyl acetate=19/1→3/1)

Sources & evidence

ORD record
ord-9400e477aede4fe7a2eae8dd9675fc31
Source dataset
uspto-grants-2011_08
Patent number
US07998956B2

Reaction notes

Loading…