2-Oxobutanoic Acid → HCID 23114371, compound

HRID 2376413Notes

Reaction equation

HRID 2376413 reaction equation
[O:1]=[C:2]([CH2:6][CH3:7])[C:3](O)=[O:4].C(Cl)(=O)C(Cl)=O.[CH:14]([C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[C:27]3[C:28]([CH3:35])=[C:29]([NH2:34])[C:30]([CH3:33])=[C:31]([CH3:32])[C:26]=3[O:25][CH2:24]2)=[CH:19][CH:18]=1)([CH3:16])[CH3:15].C(N(CC)CC)C>C1COCC1.CN(C=O)C.O>[CH:14]([C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[C:27]3[C:28]([CH3:35])=[C:29]([NH:34][C:3](=[O:4])[C:2](=[O:1])[CH2:6][CH3:7])[C:30]([CH3:33])=[C:31]([CH3:32])[C:26]=3[O:25][CH2:24]2)=[CH:19][CH:18]=1)([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 582-Oxobutanoic AcidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11630748HCID 11630748, compound

Product 1

HCID 23114371HCID 23114371, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-oxobutanoic acid (259 mg, 2.54 mmol) in THF (5 mL) was added dropwise with ice-cooling oxalyl chloride (0.33 mL, 3.80 mmol) and added DMF (three drops), and the mixture was stirred for 30 minutes. The reaction solution was warmed to room temperature and stirred at the same temperature for 1 hour, and then the solvent was distilled off under reduced pressure. The residue was dissolved in dichloromethane (5 mL) and the product was added dropwise with ice-cooling to a solution of 3-(4-isopropylphenyl)-4,6,7-trimethyl-2,3-dihydro-1-benzofuran-5-amine (500 mg, 1.69 mmol) obtained in Reference Example 30 and triethylamine (0.24 mL, 1.69 mmol) in THF (5 mL), and the resulting mixture was stirred for 30 minutes. After the reaction solution was warmed to room temperature, water was added to the reaction solution and the product was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate 2:1) to obtain 363 mg (yield: 57%) of the title compound. Yield: 57%. Melting point: 97-98° C. (ethyl acetate-hexane).

Workup

  1. stirringstirred at the same temperature for 1 hour
  2. distillationthe solvent was distilled off under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane (5 mL)
  4. additionthe product was added dropwise with ice-
  5. stirringthe resulting mixture was stirred for 30 minutes
  6. temperatureAfter the reaction solution was warmed to room temperature
  7. extractionthe product was extracted with ethyl acetate
  8. washThe organic layer was washed with water and saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate 2:1)

Sources & evidence

ORD record
ord-231df9f00d7a433aa632adfa1d1fbd7b
Source dataset
uspto-grants-2008_12
Patent number
US07465815B2

Reaction notes

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