Water → 4-(7-Methoxy-4-methylisoquinolin-3-yl)benzoic acid

HRID 2201480Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2201480
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([C:11]=1[CH3:12])=[CH:9][CH:8]=[C:7]([O:13][CH3:14])[CH:6]=2.[C:15]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)([OH:17])=[O:16].C([O-])([O-])=O.[K+].[K+].O>COCCOCCO.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCOC(C)=O>[CH3:14][O:13][C:7]1[CH:6]=[C:5]2[C:10]([C:11]([CH3:12])=[C:2]([C:21]3[CH:22]=[CH:23][C:18]([C:15]([OH:17])=[O:16])=[CH:19][CH:20]=3)[N:3]=[CH:4]2)=[CH:9][CH:8]=1

Komponenten

8

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 866980743-Chloro-7-methoxy-4-methylisoquinoline2×

Produkt 1

HCID 679748914-(7-Methoxy-4-methylisoquinolin-3-yl)benzoic acidAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 49835946Degme H2OLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a mixture of 3-chloro-7-methoxy-4-methylisoquinoline (Intermediate 15) (470 mg, 2.27 mmol), 4-carboxyphenylboronic acid (451 mg, 2.72 mmol) and K2CO3 (627 mg, 4.54 mmol) in DEGME/H2O (7 mL/1 mL) was added Pd(dppf)Cl2 (40.8 mg, 0.050 mmol) under N2 atmosphere. Then the mixture was heated to 120° C. for 16 hours. H2O (30 mL) was added, and the resulting mixture was extracted with EtOAc (15 mL×2). The aqueous layer was neutralized with 1N aqueous HCl to pH=7, extracted with EtOAc (20 mL×3). The combined organic layers were washed with H2O (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated. Purification by silica gel column (PE/EtOAc=20/1 to 1/1, then EtOAc) gave 4-(7-methoxy-4-methylisoquinolin-3-yl)benzoic acid (85.0 mg, yield 13%).

Aufarbeitung

  1. extractionthe resulting mixture was extracted with EtOAc (15 mL×2)
  2. extractionextracted with EtOAc (20 mL×3)
  3. washThe combined organic layers were washed with H2O (20 mL) and brine (20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel column (PE/EtOAc=20/1 to 1/1

Quellen und Nachweise

ORD-Eintrag
ord-2b6dbb9351274b6a9c3a2c01995f15be
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09364481B2

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