Dimethylformamide → Methyl 2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate

HRID 219916Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 219916
[CH3:1][O:2][CH2:3][C:4]1[CH:9]=[C:8]([C:10]([OH:12])=O)[CH:7]=[CH:6][C:5]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:31][C:32](=[N:44]O)[C:33]1[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[C:35]([F:43])[CH:34]=1>C1(C)C=CC=CC=1>[F:43][C:35]1[CH:34]=[C:33]([C:32]2[N:31]=[C:10]([C:8]3[CH:7]=[CH:6][C:5]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[CH3:19])=[C:4]([CH2:3][O:2][CH3:1])[CH:9]=3)[O:12][N:44]=2)[CH:42]=[CH:41][C:36]=1[C:37]([O:39][CH3:40])=[O:38]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 594958222-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 76644654Methyl 4-[amino(hydroxyimino)methyl]-2-fluorobenzoate

Produkt 1

HCID 66678608Methyl 2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoateAusbeute 82,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel3×

Versuchsvorschrift

Intermediate 28 (4 g; 15.61 mmol) was dissolved in dry Toluene (60 mL) under N2 at RT, then oxalyl chloride (1.98 mL; 23.41 mmol) was added in one portion and then DMF (24.02 μl) was added. The reaction mixture was stirred at RT for 3 hours. The reaction mixture was concentrated to afford a yellow liquid. To a flask containing Intermediate 1 (3.31 g; 15.61 mmol) in Py (20 mL; 5 V) and toluene (20 mL) at RT and under N2 was added dropwise the yellow liquid obtained previously in toluene (40 mL), the addition took 15 min. The reaction mixture was stirred at RT for 12 hours. Then the mixture was refluxed for 24 hours. The reaction mixture was cooled to RT and concentrated affording a beige solid which was washed with MeOH (40 mL). The suspension was filtered affording the title compound as a beige solid (5.58 g, 82%). 1H NMR (DMSO-d6, 300 MHz) δ 8.33 (m, 1H), 8.19-7.98 (m, 4H), 7.44-7.28 (m, 4H), 7.16-7.13 (m, 1H), 4.24-4.14 (m, 2H), 3.91 (s, 3H), 3.25 (s, 3H), 2.03 (s, 3H). LC/MS (Method B): 433.1 (M+H)+ HPLC: Rt 5.94 min (Purity: 94.9%).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. customto afford a yellow liquid
  3. additionunder N2 was added dropwise the yellow liquid
  4. additionthe addition
  5. waittook 15 min
  6. stirringThe reaction mixture was stirred at RT for 12 hours
  7. temperatureThen the mixture was refluxed for 24 hours
  8. temperatureThe reaction mixture was cooled to RT
  9. concentrationconcentrated
  10. customaffording a beige solid which
  11. washwas washed with MeOH (40 mL)
  12. filtrationThe suspension was filtered

Quellen und Nachweise

ORD-Eintrag
ord-fbfbc5b8955445178ae2b4742beae371
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202865B2

Notizen zur Reaktion

Wird geladen…