Dichloromethane → Tert-butyl 4-(2-fluorobenzoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

HRID 70190

Reaktionsgleichung

Reaktionsgleichung von HRID 70190
ClCCl.Cl[C:5]1[C:6]([F:34])=[C:7]([CH:31]=[CH:32][CH:33]=1)[C:8]([N:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH:11]1[CH2:23][O:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=1)=[O:9].C1(B(O)O)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].B(O)O>C1(C)C=CC=CC=1.O1CCOCC1.[Pd].O>[F:34][C:6]1[CH:5]=[CH:33][CH:32]=[CH:31][C:7]=1[C:8]([N:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:12][CH:11]1[CH2:23][O:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=1)=[O:9]

Komponenten

10

Edukt 5

HCID 6344DichloromethaneHCID 10340Sodium Carbonate3×HCID 61668Boronic Acid2×HCID 66827Phenylboronic AcidHCID 59671574Tert-butyl 4-(3-chloro-2-fluorobenzoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

Produkt 1

HCID 66796871Tert-butyl 4-(2-fluorobenzoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylateAusbeute 28,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 23938PalladiumKatalysator2×HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

[1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (18 mg, 0.022 mmol) was added to a mixture of tert-butyl 4-(3-chloro-2-fluorobenzoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate (100 mg, 0.222 mmol), benzeneboronic acid (81 mg, 0.67 mmol) and sodium carbonate (71 mg, 0.67 mmol) in toluene (4 mL), 1,4-dioxane (1 mL), and water (1 mL). The reaction mixture was heated to 110° C. overnight. Additional portions of the palladium catalyst, boronic acid and sodium carbonate were added and heating continued at 110° C. After stirring overnight, additional portions of the palladium catalyst, boronic acid and sodium carbonate were again added and heating continued at 110° C. overnight. Upon cooling to room temperature, the reaction mixture was filtered through Celite®, concentrated under reduced pressure, and purified by HPLC (10 to 90% MeCN/0.1% TFA in H2O/0.1% TFA gradient). This gave 115 mg (86%) of the title compound as the TFA salt that was ˜80% pure by LC-MS. LC-MS: RT=9.06 min, [M+H]+=492.9. 26.3 mg (22%) of tert-butyl 4-(2-fluorobenzoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate were also isolated as the TFA salt. LC-MS: RT=7.53 min, [M+H]+=416.7.

Aufarbeitung

  1. temperatureheating
  2. customcontinued at 110° C
  3. temperatureheating
  4. waitcontinued at 110° C. overnight
  5. temperatureUpon cooling to room temperature
  6. filtrationthe reaction mixture was filtered through Celite®
  7. concentrationconcentrated under reduced pressure
  8. custompurified by HPLC (10 to 90% MeCN/0.1% TFA in H2O/0.1% TFA gradient)

Quellen und Nachweise

ORD-Eintrag
ord-f9840a0e784c469d8ecd3489fe4ceac4
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822472B2

Verknüpfte Notizen

Wird geladen…