Triethylamine → 2-(2-Chloro-phenyl)-4-ethyl-oxazole-5-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester

HRID 2236177Notes

Reaction equation

HRID 2236177 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[C:4]([NH:6][CH:7]([CH2:11][CH3:12])[C:8]([OH:10])=O)=O.C(Cl)(=O)[C:18](Cl)=[O:19].C(N(CC)CC)C.[OH:30][N:31]1[C:35](=[O:36])[CH2:34][CH2:33][C:32]1=[O:37]>O1CCCC1>[O:37]=[C:32]1[CH2:33][CH2:34][C:35](=[O:36])[N:31]1[O:30][C:18]([C:8]1[O:10][C:4]([C:3]2[CH:13]=[CH:14][CH:15]=[CH:16][C:2]=2[Cl:1])=[N:6][C:7]=1[CH2:11][CH3:12])=[O:19]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 80170N-HydroxysuccinimideHCID 242068382-(2-Chloro-benzoylamino)-butyric acid

Product 1

HCID 593013122-(2-Chloro-phenyl)-4-ethyl-oxazole-5-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl esterYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred slurry of 2-(2-chloro-benzoylamino)-butyric acid (2.84 g, 11.8 mmol) in 60 mL of anhydrous tetrahydro furan, was added oxalyl chloride (10.1 mL, 118 mmol). The mixture was stirred at 50° C. overnight and then the solvent was evaporated in vacuo. The oily residue was treated with toluene and evaporated to remove trace of oxalyl chloride. The residue was then cooled in an ice bath and triethylamine (3.4 mL, 23.6 mmol) was added followed by the addition of 1-hydroxy-pyrrolidine-2,5-dione. The reaction mixture was stirred at 50° C. overnight before the solvent was removed in vacuo. The residue was then purified by flash chromatography (Merck silica gel 60, 230-400 mesh, 5-60% ethyl acetate in hexane for 25 min) to give 2-(2-chloro-phenyl)-4-ethyl-oxazole-5-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester (997 mg, 25% yield) as a light yellow solid. LCMS calcd for C16H13ClN2O5 (m/e) 348, obsd 349 (M+H).

Workup

  1. customthe solvent was evaporated in vacuo
  2. additionThe oily residue was treated with toluene
  3. customevaporated
  4. customto remove trace of oxalyl chloride
  5. temperatureThe residue was then cooled in an ice bath
  6. stirringThe reaction mixture was stirred at 50° C. overnight before the solvent
  7. customwas removed in vacuo
  8. customThe residue was then purified by flash chromatography (Merck silica gel 60, 230-400 mesh, 5-60% ethyl acetate in hexane for 25 min)

Sources & evidence

ORD record
ord-34b268a9426c46fbb4704e275f5d2405
Source dataset
uspto-grants-2010_05
Patent number
US07714126B2

Reaction notes

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