Acetic Acid → HCID 67125874, compound

HRID 929986Notes

Reaction equation

HRID 929986 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[C:16]([CH3:23])[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CC(O)=O>C(Cl)Cl.[Zn]>[NH2:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:11]([NH:10][C:7]2[CH:6]=[C:5]([C:1]([CH3:3])([CH3:2])[CH3:4])[O:9][N:8]=2)=[O:12])=[CH:15][C:16]=1[CH3:23]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 67125868HCID 67125868, compound

Product 1

HCID 67125874HCID 67125874, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of crude 1-(5-tert-butylisoxazol-3-yl)-3-(3-methyl-4-nitrophenyl)urea (2.0 g, 6.1 mmol) from Step 1 of this example in DCM (10 mL) was added AcOH (1.8 mL, 31.2 mmol), followed by zinc (1.99 g, 31.2 mmol) in small portions. The resulting mixture was stirred at rt for 1 h. LC-MS indicated that the reaction was complete. The reaction mixture was carefully quenched with sat. NaHCO3 (50 mL) at rt, and the resulting biphasic mixture was extracted with EtOAc (50 mL). The organic layer was washed with brine (20 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography, eluting with 0-65% EtOAc in hexanes, to give 1-(4-amino-3-methylphenyl)-3-(5-tert-butylisoxazol-3-yl)urea (560 mg, 61% over two steps). LC-MS (ESI) m/z 289 (M+H)+.

Workup

  1. customThe reaction mixture was carefully quenched with sat. NaHCO3 (50 mL) at rt
  2. extractionthe resulting biphasic mixture was extracted with EtOAc (50 mL)
  3. washThe organic layer was washed with brine (20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography
  8. washeluting with 0-65% EtOAc in hexanes

Sources & evidence

ORD record
ord-74417968e3a243e8826d2f552311a822
Source dataset
uspto-grants-2016_03
Patent number
US09296722B2

Reaction notes

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