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

HRID 1172964노트

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HRID 1172964 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 1049Pyridine용매

반응 조건

온도
200 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-af40b097ce7b41bf802930622b34f709
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834039B2

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