Hydroxylamine → Ethyl 3-(4-(N-(3-chloro-4-fluorophenyl)-N'-hydroxycarbamimidoyl)-1,2,5-oxadiazol-3-yl)propanoate

HRID 2097658Notes

Reaction equation

HRID 2097658 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2[C:13]([CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N:14][O:15][N:16]=2)=O)[CH:5]=[CH:6][C:7]=1[F:8].P(Cl)(Cl)(Cl)(Cl)Cl.[NH2:30][OH:31]>C1C=CC=CC=1.CO>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2[C:13]([CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N:14][O:15][N:16]=2)=[N:30][OH:31])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 3

HCID 787HydroxylamineHCID 24819Phosphorus pentachlorideHCID 58941764Ethyl 3-(4-[(3-chloro-4-fluorophenyl)amino]carbonyl-1,2,5-oxadiazol-3-yl)propanoate

Product 1

HCID 178471190Ethyl 3-(4-(N-(3-chloro-4-fluorophenyl)-N'-hydroxycarbamimidoyl)-1,2,5-oxadiazol-3-yl)propanoateYield 30.2%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 887MethanolSolvent

Procedure

Ethyl 3-(4-[(3-chloro-4-fluorophenyl)amino]carbonyl-1,2,5-oxadiazol-3-yl)propanoate (27 mg, 0.079 mmol) was suspended in benzene (1 mL) under an atmosphere of nitrogen and phosphorus pentachloride (18.0 mg, 0.086 mmol) was added. The solution was heated to reflux for 2.5 h. The solvent was removed in vacuo. The residue was dissolved in EtOH (1.0 mL) and hydroxylamine (100 μL, 2 mmol) (50% solution in water) was added to the reaction. After stirring 1 h, the solution was diluted with MeOH and purified by preparative LCMS to give the desired product (8.5 mg, 30%). 1H NMR (400 MHz, CD3OD): δ 7.03 (t, J=8.9 Hz, 1H), 6.95 (dd, J=6.4, 2.7 Hz, 1H), 6.71 (m, 1H), 4.12 (q, J=7.2 Hz, 2H), 3.11 (t, J=7.2 Hz, 2H), 2.80 (t, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H); LCMS for C14H15ClFN4O4 (M+H)+: m/z=357.1.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 2.5 h
  3. customThe solvent was removed in vacuo
  4. dissolutionThe residue was dissolved in EtOH (1.0 mL)
  5. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-8e0eb1447d4647b692bd301e740bae9b
Source dataset
uspto-grants-2013_05
Patent number
US08450351B2

Reaction notes

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