Tetrahydrofuran → Methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoate

HRID 75820Notes

Reaction equation

HRID 75820 reaction equation
[CH3:1][CH:2]([CH3:25])[CH:3]([NH:8][C:9]([C:11]1[O:15][N:14]=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=2)[CH:12]=1)=[O:10])[C:4]([O:6][CH3:7])=[O:5].C1COCC1.[Cl-].[NH4+]>CCO.O.[Fe]>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([C:13]2[CH:12]=[C:11]([C:9]([NH:8][CH:3]([CH:2]([CH3:25])[CH3:1])[C:4]([O:6][CH3:7])=[O:5])=[O:10])[O:15][N:14]=2)=[CH:17][CH:18]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 67352411HCID 67352411, compound

Product 1

HCID 67352790Methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoateYield 65.7%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

Methyl 3-methyl-2-(3-(4-nitrophenyl)isoxazole-5-carboxamido)butanoate (2 g) was dissolved in EtOH (20 ml), THF (8 ml), and water (8 ml). Then ammonium chloride (925 mg) and Iron (756 mg) was added and refluxed at 80° C. for 3 h. The reaction mixture was cooled, filtered through celite and solvent removed under reduced pressure to get dark brown residue. Residue was taken in water and extracted with ethyl acetate, organic layer separated, dried over Na2SO4 and concentrated to get dark brown residue which was purified by silica gel column chromatography in 1:1 EtOAc:Pet ether to get yellow solid which was crystallized from methylene chloride/Pet ether to yield 1.2 g (65%) pale yellow solid. MS (ES+): m/z 318 (M+1); 1HNMR (DMSO-d6, 300 MHz): δ 9.1 (d, 1H), 7.55 (d, 2H), 7.51 (s, 1H), 6.63 (d, 2H), 5.63 (bs, 1H), 4.27 (m, 1H), 3.65 (s, 3H), 2.19 (m, 1H), 0.94 (d, 6H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered through celite and solvent
  3. customremoved under reduced pressure
  4. customto get dark brown residue
  5. extractionextracted with ethyl acetate, organic layer
  6. customseparated
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto get dark brown residue which
  10. customwas purified by silica gel column chromatography in 1:1 EtOAc
  11. customPet ether to get yellow solid which
  12. customwas crystallized from methylene chloride/Pet ether

Sources & evidence

ORD record
ord-d801519dc61941dca43196867ee85ae7
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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