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

HRID 1845787Notes

Reaction equation

HRID 1845787 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, 1 H), 6.95 (dd, J=6.4, 2.7 Hz, 1 H), 6.71 (m, 1 H), 4.12 (q, J=7.2 Hz, 2 H), 3.11 (t, J=7.2 Hz, 2 H), 2.80 (t, J=7.2 Hz, 2 H), 1.23 (t, J=7.2 Hz, 3 H); LCMS for C14H15ClFN4O1(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-62ae1d9afd7d4ec294dee59257958f35
Source dataset
uspto-grants-2015_02
Patent number
US08951536B2

Reaction notes

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