Nitrogen → 4-Methyl-3-[3-(2,3,4-trihydroxy-phenyl)-acryloylamino]-benzoic acid methyl ester

HRID 383591

Reaktionsgleichung

Reaktionsgleichung von HRID 383591
N#N.[CH3:3][O:4][C:5](=[O:30])[C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:29])[CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23]C)=[C:19]([O:25]C)[C:18]=2[O:27]C)[CH:7]=1.B(Br)(Br)Br.O>C(Cl)Cl.CO>[CH3:12][C:9]1[CH:10]=[CH:11][C:6]([C:5]([OH:30])=[O:4])=[CH:7][C:8]=1[NH:13][C:14](=[O:29])[CH:15]=[CH:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([OH:25])[C:18]=1[OH:27].[CH3:3][O:4][C:5](=[O:30])[C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:29])[CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([OH:25])[C:18]=2[OH:27])[CH:7]=1

Komponenten

8

Edukt 4

HCID 947NitrogenHCID 962WaterHCID 25134Boron tribromideHCID 52034944-Methyl-3-[3-(2,3,4-trimethoxy-phenyl)-acryloylamino]-benzoic acid methyl ester

Produkt 2

HCID 725705854-Methyl-3-[3-(2,3,4-trihydroxy-phenyl)-acryloylamino]-benzoic acid methyl esterAusbeute 25 %HCID 725705884-Methyl-3-[3-(2,3,4-trihydroxy-phenyl)-acryloylamino]-benzoic acidAusbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve anilide (53) (40 mg, 0.10 mmol) in anhydrous DCM (1.3 mL) at −78° C., add dropwise a 1M solution of BBr3 in DCM (830 μL, 0.83 mmol) and stir for additional 30 min at −78° C. After slowly warming up stir the reaction solution for additional 4 h at rt. Cool reaction mixture to 0° C., add dropwise water and DCM under vigorous stirring followed by MeOH to homogenize the mixture. Partition the hydrolized reaction mixture between water and EtOAc, extract the aqu. layer with EtOAc (3×), wash combined organic layer with brine and dry it with Na2SO4. Purify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95) to obtain 4-Methyl-3-[3-(2,3,4-trihydroxy-phenyl)-acryloylamino]-benzoic acid (54) (6.5 mg, 19%) as an yellowish solid and 4-Methyl-3-[3-(2,3,4-trihydroxy-phenyl)-acryloylamino]-benzoic acid methyl ester (55) (9 mg, 25%) as an yellowish solid. 1H NMR (400 MHz, CD3OD) (54): 2.40 (s, 3H); 6.43 (d, 1H, J=8.6 Hz); 6.90 (d, 1H, J=15.6 Hz); 6.97 (d, 1H, J=8.6 Hz); 7.40 (d, 1H, J=8.1 Hz); 7.83 (dd, 1H, J1=8.1 Hz, J2=1.5 Hz); 7.93 (d, 1H, J=15.6 Hz); 8.17 (br.s, 1H); (55): 2.40 (s, 3H); 3.93 (s, 3H); 6.43 (d, 1H, J=8.6 Hz); 6.90 (d, 1H, J=15.7 Hz); 6.97 (d, 1H, J=8.6 Hz); 7.40 (d, 1H, J=8.1 Hz); 7.82 (dd, 1H, J1=7.8 Hz, J2=1.7 Hz); 7.93 (d, 1H, J=15.9 Hz); 8.18 (br.s, 1H).

Aufarbeitung

  1. custom(The following reaction
  2. temperatureAfter slowly warming up
  3. stirringstir the reaction solution for additional 4 h at rt
  4. temperatureCool
  5. customreaction mixture to 0° C.
  6. stirringunder vigorous stirring
  7. stirringto homogenize the mixture
  8. customPartition the hydrolized reaction mixture between water and EtOAc
  9. extractionextract the aqu
  10. washlayer with EtOAc (3×), wash
  11. dry with materialdry it with Na2SO4
  12. customPurify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95)

Quellen und Nachweise

ORD-Eintrag
ord-0d47767e40cd44aca33c9da71ec7778b
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367677B2

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