Water → Ethyl 3-(4-amino-3-methylphenyl)isoxazole-5-carboxylate

HRID 75801Notes

Reaction equation

HRID 75801 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:11]2[CH:15]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[O:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O.[Cl-].[NH4+].O1CCCC1.O>C(O)C.[Fe]>[NH2:8][C:7]1[CH:6]=[CH:5][C:4]([C:11]2[CH:15]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[O:13][N:12]=2)=[CH:3][C:2]=1[CH3:1]

Participants

7

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 67352122Ethyl 3-(3-methyl-4-nitrophenyl)isoxazole-5-carboxylate

Product 1

HCID 67353967Ethyl 3-(4-amino-3-methylphenyl)isoxazole-5-carboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 3-(3-methyl-4-nitrophenyl)isoxazole-5-carboxylate (1.0 equiv.), iron powder (2.0 equiv.), and ammonium chloride (3.0 equiv.) in a mixture of ethanol, tetrahydrofuran and water (4:2:1) were heated to 80° C. for 9 hours. Reaction mixture was cooled and filtered through celite. The filtrate was evaporated to dryness under vacuum and the residue was diluted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel, eluting with 0-2% acetone in chloroform, to provide the title compound as a pale green solid (81%); 1H NMR (300 MHz, DMSO-d6) δ: 1.28-1.33 (t, J=7.2 Hz, 3H), 2.07 (s, 3H), 4.31-4.38 (q, 2H), 5.38 (s, 2H), 6.62-6.65 (d, J=8.4 Hz, 1H), 7.45-7.48 (dd, J=8.1 Hz, 1.8 Hz, 1H), 7.52 (s, 1H), 7.63 (s, 1H); IR (KBr) 3490, 3381, 3135, 2975, 2905, 1725, 1628, 1606, 1471, 1417, 1381, 1279, 1134, 1027, 924, 828, 769 cm−1.

Workup

  1. customReaction mixture
  2. temperaturewas cooled
  3. filtrationfiltered through celite
  4. customThe filtrate was evaporated to dryness under vacuum
  5. additionthe residue was diluted with EtOAc
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography on silica gel
  11. washeluting with 0-2% acetone in chloroform

Sources & evidence

ORD record
ord-4f7889700d604d2696aabf845fd6f2da
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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