3-chloro-N'-hydroxy-4-propan-2-yloxybenzenecarboximidamide → 3-(3-Chloro-4-isopropoxyphenyl)-5-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1,2,4-oxadiazole

HRID 1172963Notes

Reaction equation

HRID 1172963 reaction equation
[CH3:1][C:2]1([CH3:18])[O:6][CH:5]([CH2:7][O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=2)[CH2:4][O:3]1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1[O:30][CH:31]([CH3:33])[CH3:32])/[C:23](=[N:25]/O)/[NH2:24]>N1C=CC=CC=1>[Cl:19][C:20]1[CH:21]=[C:22]([C:23]2[N:25]=[C:13]([C:12]3[CH:16]=[CH:17][C:9]([O:8][CH2:7][CH:5]4[CH2:4][O:3][C:2]([CH3:18])([CH3:1])[O:6]4)=[CH:10][CH:11]=3)[O:14][N:24]=2)[CH:27]=[CH:28][C:29]=1[O:30][CH:31]([CH3:33])[CH3:32]

Participants

4

Reactant 2

HCID 595565653-chloro-N'-hydroxy-4-propan-2-yloxybenzenecarboximidamideHCID 595567154-((2,2-Dimethyl-1,3-dioxolan-4-yl)methoxy)benzoyl chloride

Product 1

HCID 595565303-(3-Chloro-4-isopropoxyphenyl)-5-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1,2,4-oxadiazoleYield 56.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
200 °C

Procedure

In a 25 mL microwave tube 4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzoyl chloride (0.483 g, 1.784 mmol) and (Z)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (0.272 g, 1.189 mmol) in pyridine (15 mL) were combined to give an orange solution. The vessel was capped and the reaction heated at 200° C. for 20 min under microwave irradiation (Biotage Optimizer, 300 W). The mixture was cooled, the solvent was removed to afford a yellow solid, which was partitioned between water (100 mL) and EtOAc (50 mL), extracted by EtOAc (2×30 mL), the combined EtOAC layer was washed by water (2×30 mL), and concentrated to afford a yellow solid, which was purified via silica gel chromatography (40 g, 30% EtOAc:Heptane) to afford 3-(3-chloro-4-isopropoxyphenyl)-5-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1,2,4-oxadiazole (0.3 g, 0.674 mmol, 56.7% yield) as white solid. LC/MS (30—95 NH4OAc 4m GC8.olp) Rt=3.22 min.; MS m/z: 445.31 (M+H)+. 1H NMR (400 MHz, Solvent d-DMSOδ ppm 8.17-8.09 (m, 2H), 8.05 (d, J=2.13 Hz, 1H), 7.99 (dd, J=8.64, 2.15 Hz, 1H), 7.38 (d, J=9.01 Hz, 1H), 7.26-7.19 (m, 2H), 4.88-4.77 (m, 1H), 4.45 (s, 1H), 4.23-4.07 (m, 3H), 3.79 (dd, J=8.42, 6.29 Hz, 1H), 1.35 (m, 12H).

Workup

  1. customto give an orange solution
  2. customThe vessel was capped
  3. temperatureThe mixture was cooled
  4. customthe solvent was removed
  5. customto afford a yellow solid, which
  6. customwas partitioned between water (100 mL) and EtOAc (50 mL)
  7. extractionextracted by EtOAc (2×30 mL)
  8. washthe combined EtOAC layer was washed by water (2×30 mL)
  9. concentrationconcentrated
  10. customto afford a yellow solid, which
  11. customwas purified via silica gel chromatography (40 g, 30% EtOAc:Heptane)

Sources & evidence

ORD record
ord-fdaab70e3e3e47b996f6ccaafd08950a
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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