Oxalyl chloride → N-(6-acetyl-2-chloro-3-methoxyphenyl)-5-isopropylisoxazole-3-carboxamide

HRID 1675430Notes

Reaction equation

HRID 1675430 reaction equation
[CH:1]([C:4]1[O:8][N:7]=[C:6]([C:9]([OH:11])=O)[CH:5]=1)([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[C:24]([Cl:25])=[C:23]([O:26][CH3:27])[CH:22]=[CH:21][C:20]=1[C:28](=[O:30])[CH3:29].C([O-])(O)=O.[Na+]>C(Cl)Cl.O1CCOCC1.CN(C=O)C>[C:28]([C:20]1[C:19]([NH:18][C:9]([C:6]2[CH:5]=[C:4]([CH:1]([CH3:2])[CH3:3])[O:8][N:7]=2)=[O:11])=[C:24]([Cl:25])[C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)(=[O:30])[CH3:29]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 64838125-(Propan-2-yl)-1,2-oxazole-3-carboxylic acidHCID 299199881-(2-Amino-3-chloro-4-methoxyphenyl)ethanone

Product 1

HCID 66650637N-(6-acetyl-2-chloro-3-methoxyphenyl)-5-isopropylisoxazole-3-carboxamideYield 60%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 5-isopropylisoxazole-3-carboxylic acid (3.5 g, 22.6 mmol) in DCM (35 mL) was added anhydrous DMF (few drops) and oxalyl chloride (3.82 mL, 43.2 mmol) at 0° C. under nitrogen. At the end of the gas escape, the reaction mixture was allowed to warm up to room temperature. The mixture was stirred at room temperature for 2 hrs and was evaporated. Dioxane (70 mL) was added under nitrogen, followed by a solution of 1-(2-amino-3-chloro-4-methoxy-phenyl)-ethanone 40d (4.10 g, 20.6 mmol) in dioxane (15 mL). The reaction mixture was stirred at room temperature for 16 hrs. NaHCO3 was then added. The mixture was extracted with EtOAc. Organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was triturated in Et2O to yield compound 92d as a brown solid in 60% yield.

Workup

  1. customwas evaporated
  2. additionDioxane (70 mL) was added under nitrogen
  3. stirringThe reaction mixture was stirred at room temperature for 16 hrs
  4. extractionThe mixture was extracted with EtOAc
  5. dry with materialOrganics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was triturated in Et2O

Sources & evidence

ORD record
ord-22b788f9c20a4ba3bfb8cfba50222359
Source dataset
uspto-grants-2011_08
Patent number
US08003659B2

Reaction notes

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