Sodium Carbonate → 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'-methyl Ester

HRID 2428183Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2428183
[CH3:1][O:2][C:3]([C:5]1[CH2:6][N:7]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:8][CH2:9][C:10]=1OS(C(F)(F)F)(=O)=O)=[O:4].[Cl:26][C:27]1[C:32]([F:33])=[CH:31][CH:30]=[C:29]([F:34])[C:28]=1[C:35]1[CH:39]=[C:38]([CH2:40][O:41][C:42]2[CH:47]=[CH:46][C:45](B3OC(C)(C)C(C)(C)O3)=[CH:44][N:43]=2)[O:37][N:36]=1.C([O-])([O-])=O.[Na+].[Na+]>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>[CH3:1][O:2][C:3]([C:5]1[CH2:6][N:7]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:8][CH2:9][C:10]=1[C:45]1[CH:44]=[N:43][C:42]([O:41][CH2:40][C:38]2[O:37][N:36]=[C:35]([C:28]3[C:29]([F:34])=[CH:30][CH:31]=[C:32]([F:33])[C:27]=3[Cl:26])[CH:39]=2)=[CH:47][CH:46]=1)=[O:4]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 152219361-Tert-butyl 3-methyl 4-(trifluoromethanesulfonyloxy)-1,2,5,6-tetrahydropyridine-1,3-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 671489026-[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'-methyl EsterAusbeute 53,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957; 6.04 g, 15.5 mmol), 2-[3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (9.28 g, 20.7 mmol) and aq. 2M Na2CO3 (93.1 mL, 186 mmol) in DME (150 mL) was prepared, and Pd(PPh3)4 (1.00 g, 0.866 mmol) was added in portions. The mixture was heated to 80° C., and stirred at this temperature for 1 h. The mixture was allowed to cool to rt, and was diluted with EtOAc. The resulting mixture was washed with water and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:2→2:1) yielded the title compound (4.64 g, 40%). LC-MS: tR=1.34 min; ES+: 562.34.

Aufarbeitung

  1. customwas prepared
  2. temperatureto cool to rt
  3. washThe resulting mixture was washed with water and brine
  4. dry with materiallayer was dried over MgSO4
  5. filtrationfiltered
  6. customthe solvents were removed under reduced pressure
  7. customPurification of the residue by FC (EtOAc/heptane 1:2→2:1)

Quellen und Nachweise

ORD-Eintrag
ord-7104ad02ea224b4daa9864b15315c645
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07968720B2

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