Nitrogen → 6-[3-(2-Chloro-3,6-difluoro-phenyl)isoxazol-5-ylmethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic Acid 1'-tert-butyl Ester 3'-ethyl Ester

HRID 2428190Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2428190
[CH2:1]([O:3][C:4]([C:6]1[CH2:7][N:8]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:9][CH2:10][C:11]=1OS(C(F)(F)F)(=O)=O)=[O:5])[CH3:2].[Cl:27][C:28]1[C:33]([F:34])=[CH:32][CH:31]=[C:30]([F:35])[C:29]=1[C:36]1[CH:40]=[C:39]([CH2:41][O:42][C:43]2[CH:48]=[CH:47][C:46](B3OC(C)(C)C(C)(C)O3)=[CH:45][N:44]=2)[O:38][N:37]=1.C([O-])([O-])=O.[Na+].[Na+].N#N>COCCOC.CCOC(C)=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>[CH2:1]([O:3][C:4]([C:6]1[CH2:7][N:8]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:9][CH2:10][C:11]=1[C:46]1[CH:45]=[N:44][C:43]([O:42][CH2:41][C:39]2[O:38][N:37]=[C:36]([C:29]3[C:30]([F:35])=[CH:31][CH:32]=[C:33]([F:34])[C:28]=3[Cl:27])[CH:40]=2)=[CH:48][CH:47]=1)=[O:5])[CH3:2]

Komponenten

8

Edukt 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 222284091-(tert-Butyl) 3-ethyl 4-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1,3(2H)-dicarboxylateHCID 671487962-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine

Produkt 1

HCID 671489856-[3-(2-Chloro-3,6-difluoro-phenyl)isoxazol-5-ylmethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic Acid 1'-tert-butyl Ester 3'-ethyl EsterAusbeute 62,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Compound A2 (9.52 g, 23.6 mmol) and 2-[3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (13.2 g, 29.5 mmol) were dissolved in DME (164 mL), and aq. 2M Na2CO3 (118 mL) was added. The mixture was degassed with N2 (5 min), and Pd(PPh3)4 (1.36 g, 1.18 mmol) was added. The mixture was heated rapidly to 80° C., and was stirred at this temperature for 1 h. The mixture was allowed to cool to rt, and was diluted with EtOAc (200 mL). The mixture was washed with water (200 mL). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane→EtOAc/heptane 30:70) yielded the title compound (8.45 g, 62%). LC-MS: tR=1.13 min, ES+: 576.41.

Aufarbeitung

  1. additionwas added
  2. temperatureto cool to rt
  3. washThe mixture was washed with water (200 mL)
  4. dry with materiallayer was dried over MgSO4
  5. filtrationfiltered
  6. customthe solvents were removed under reduced pressure
  7. customPurification of the crude by FC (heptane→EtOAc/heptane 30:70)

Quellen und Nachweise

ORD-Eintrag
ord-7e9dca83f617441ea03c8f72561a3acb
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07968720B2

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