Sodium Bicarbonate → 3-Chloro-4-(5-fluoro-6-hydroxyquinolin-2-yl)benzoic acid

HRID 2201483Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2201483
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:13])[C:8]=2[F:12])[N:3]=1.B([C:17]1[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][C:18]=1[Cl:26])(O)O.C([O-])(O)=O.[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:26][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:17]=1[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:13])[C:8]=2[F:12])[N:3]=1)[C:21]([OH:23])=[O:22]

Komponenten

6

Edukt 3

HCID 516892Sodium BicarbonateHCID 17750227SimtuzumabHCID 866980752-Chloro-5-fluoroquinolin-6-ol2×

Produkt 1

HCID 574048783-Chloro-4-(5-fluoro-6-hydroxyquinolin-2-yl)benzoic acidAusbeute 15,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

2-Chloro-5-fluoroquinolin-6-ol (Intermediate 16, 1.0 mmol) and 4-borono-3-chlorobenzoic acid (1.1 mmol) were mixed with 5% (Ph3P)4Pd and 4.0 mmol of NaHCO3 in 20 ml 50% dioxane/water. The mixture was degassed three times by evacuation and argon filling and heated at 95° C. overnight. The reaction was diluted with 20 ml of water and filtered. The filtrate was acidified with 1N HCl to pH=4. The precipitate was filtered and washed with water, dried. The crude was purified by column using AcOH/MeOH/EtOAC (1/5/94) as solvent B and hexanes as solvent A with gradient 2 to 100%. The fractions with compound were pooled and evaporated to obtain white solid. The solid was triturated with diisopropyl ether. 50 mg of final product was obtained. 1H-NMR (DMSO-d6, 300 MHz, TMS): δ 10.55 (b, 1H), 8.47 (d, 1H), 8.01-8.03 (m, 2H), 7.79 (m, 3H), 7.56 (t, 1H). MS (ESI): m/z=316.3 [M−1]−.

Aufarbeitung

  1. customThe mixture was degassed three times by evacuation and argon filling
  2. additionThe reaction was diluted with 20 ml of water
  3. filtrationfiltered
  4. filtrationThe precipitate was filtered
  5. washwashed with water
  6. customdried
  7. customThe crude was purified by column
  8. customevaporated
  9. customto obtain white solid
  10. customThe solid was triturated with diisopropyl ether

Quellen und Nachweise

ORD-Eintrag
ord-e6dd8eb262c046eba74489dcbc875ae3
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09364481B2

Notizen zur Reaktion

Wird geladen…