Potassium Phosphate, Tribasic → Methyl 2-{[(4-fluorophenyl)methyl]oxy}-5-(1H-pyrazol-4-yl)benzoate

HRID 1623733

Reaktionsgleichung

Reaktionsgleichung von HRID 1623733
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:10]2[CH:19]=[CH:18][C:17](I)=[CH:16][C:11]=2[C:12]([O:14][CH3:15])=[O:13])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][N:32](C(OC(C)(C)C)=O)[CH:33]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(C([O-])=O)(C)C>COCCOC.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]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:10]2[CH:19]=[CH:18][C:17]([C:29]3[CH:30]=[N:31][NH:32][CH:33]=3)=[CH:16][C:11]=2[C:12]([O:14][CH3:15])=[O:13])=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 6919101PivalateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 67106887Methyl 2-{[(4-fluorophenyl)methyl]oxy}-5-iodobenzoate

Produkt 1

HCID 67107242Methyl 2-{[(4-fluorophenyl)methyl]oxy}-5-(1H-pyrazol-4-yl)benzoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of methyl 2-{[(4-fluorophenyl)methyl]oxy}-5-iodobenzoate (may be prepared as described in Description 112; 1.4 g, 3.63 mmol) in 1,2-dimethoxyethane (40 ml) was added 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (3.20 g, 10.88 mmol), tripotassium phosphate (1.54 g, 7.25 mmol), PdCl2(dppf) (0.16 g, 0.22 mmol) and the mixture was heated to 80° C. for 6 hours. The temperature was raised to 90° C. for 2 hours. Further catalyst was added and the mixture was divided into two. One 20 ml portion was subjected to 120° C. for 30 min under microwave conditions. The second portion of 20 ml was heated to reflux for 12 hrs. The 1,1-dimethylethyl carboxylate protected products were deprotected. The products were then combined and evaporated under reduced pressure on a buchi. The mixture was taken up into dichloromethane (20 ml), treated with trifluoroacetic acid (10 ml) and stirred at room temperature for 1 hour. The mixture was evaporated and purified using the Flashmaster eluting with 0-25% methanol/dichloromethane to yield the title compound. 1.15 g.

Aufarbeitung

  1. temperatureThe temperature was raised to 90° C. for 2 hours
  2. additionFurther catalyst was added
  3. temperatureThe second portion of 20 ml was heated
  4. temperatureto reflux for 12 hrs
  5. customevaporated under reduced pressure on a buchi
  6. additiontreated with trifluoroacetic acid (10 ml)
  7. customThe mixture was evaporated
  8. custompurified
  9. washeluting with 0-25% methanol/dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-54d6cd84afab4538906a7a7634cff657
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778939B2

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