Hydrochloric Acid → 2-(4-(3-(3-Chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenoxy)acetic acid

HRID 1172964Notes

Reaction equation

HRID 1172964 reaction equation
Cl[C:2]([C:4]1[CH:18]=[CH:17][C:7]([O:8][CH2:9][C:10]([O:12]C(C)(C)C)=[O:11])=[CH:6][CH:5]=1)=[O:3].[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].Cl>N1C=CC=CC=1>[Cl:19][C:20]1[CH:21]=[C:22]([C:23]2[N:25]=[C:2]([C:4]3[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:17][CH:18]=3)[O:3][N:24]=2)[CH:27]=[CH:28][C:29]=1[O:30][CH:31]([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 595565653-chloro-N'-hydroxy-4-propan-2-yloxybenzenecarboximidamideHCID 59556633Tert-butyl 2-(4-(chlorocarbonyl)phenoxy)acetate

Product 1

HCID 595566192-(4-(3-(3-Chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenoxy)acetic acidYield 31.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
200 °C

Procedure

A 25 mL microwave reaction vial was charged with tert-butyl 2-(4-(chlorocarbonyl)phenoxy)acetate (0.815 g, 3.01 mmol) and pyridine (15 mL), (Z)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (0.459 g, 2.007 mmol) was added. 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 reaction mixture was poured into stirring HCl (10%, 100 mL), the resulting suspension was filtered, the solid was washed by HCl (5%, 2×10 mL) and dried to afford grey solid, which was purified by RP-HPLC (A=50 mM ammonium acetate, B=acetonitrile; 30-95% B over 25.0 min (21.0 mL/min flow rate); 21.2×250 mm Thermo Hyperprep C18 column, 8 μm particles) to give 2-(4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenoxy)acetic acid (0.246 g, 0.633 mmol, 31.5% yield) as white solid. LC/MS (Table 1, Method f) Rt=2.08 min.; MS m/z: 389.14 (M+H)+. 1H NMR (400 MHz, Solvent d-DMSO δ ppm 13.28-13.07 (m, 1H), 8.13 (d, J=9.03 Hz, 2H), 8.05 (d, J=2.13 Hz, 1H), 7.99 (dd, J=8.64, 2.15 Hz, 1H), 7.38 (d, J=9.04 Hz, 1H), 7.18 (d, J=9.06 Hz, 2H), 4.85 (s, 3H), 1.35 (d, J=6.03 Hz, 6H).

Workup

  1. customA 25 mL microwave reaction
  2. additionwas added
  3. customThe vessel was capped
  4. temperatureThe mixture was cooled
  5. additionthe reaction mixture was poured
  6. filtrationthe resulting suspension was filtered
  7. washthe solid was washed by HCl (5%, 2×10 mL)
  8. customdried
  9. customto afford grey solid, which
  10. customwas purified by RP-HPLC (A=50 mM ammonium acetate, B=acetonitrile

Sources & evidence

ORD record
ord-af40b097ce7b41bf802930622b34f709
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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