Sodium Carbonate → 5-(4-{(S)-1-[(S)-6-(2-hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]ethyl}-phenyl)-pyridine-2-carboxylic acid

HRID 80954

Reaktionsgleichung

Reaktionsgleichung von HRID 80954
C([O-])([O-])=O.[Na+].[Na+].[OH:7][C:8]([CH3:41])([CH3:40])[CH2:9][C@@:10]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:15][C:14](=[O:16])[N:13]([C@H:17]([C:19]2[CH:24]=[CH:23][C:22](B3OC(C)(C)C(C)(C)O3)=[CH:21][CH:20]=2)[CH3:18])[CH2:12][CH2:11]1.C[O:43][C:44]([C:46]1[CH:51]=[CH:50][C:49](Br)=[CH:48][N:47]=1)=[O:45]>CN(C)C=O>[OH:7][C:8]([CH3:40])([CH3:41])[CH2:9][C@@:10]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:15][C:14](=[O:16])[N:13]([C@H:17]([C:19]2[CH:20]=[CH:21][C:22]([C:49]3[CH:50]=[CH:51][C:46]([C:44]([OH:43])=[O:45])=[N:47][CH:48]=3)=[CH:23][CH:24]=2)[CH3:18])[CH2:12][CH2:11]1

Komponenten

5

Edukt 3

HCID 10340Sodium CarbonateHCID 7016458Methyl 5-bromopyridine-2-carboxylateHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Produkt 1

HCID 581092795-(4-{(S)-1-[(S)-6-(2-hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]ethyl}-phenyl)-pyridine-2-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

2 M aqueous Na2CO3 solution (1.3 mL) was added to a solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-{(S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-ethyl}-1,3-oxazinan-2-one (0.60 g) and 5-bromo-pyridine-2-carboxylic acid methyl ester (0.41 g) in N,N-dimethylformamide (4 mL). The resulting mixture was sparged with argon for 10 min, before [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II)dichloromethane complex (61 mg) was added. The mixture was heated to 100° C. and stirred at this temperature overnight. After cooling to ambient temperature, the mixture was diluted with ethyl acetate and extracted with water and brine. The aqueous extracts were combined, acidified (pH ca. 5-6) using citric acid, and extracted with CH2Cl2/MeOH (ca. 10:1). The combined organic extracts were washed with brine and dried (MgSO4). The solvent was removed and the residue was purified by chromatography on silica gel (CH2Cl2/MeOH 98:2→50:50) to afford the title compound as a resin-like solid.

Aufarbeitung

  1. customThe resulting mixture was sparged with argon for 10 min, before [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II)dichloromethane complex (61 mg)
  2. additionwas added
  3. temperatureAfter cooling to ambient temperature
  4. additionthe mixture was diluted with ethyl acetate
  5. extractionextracted with water and brine
  6. extractionextracted with CH2Cl2/MeOH (ca. 10:1)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. customThe solvent was removed
  10. customthe residue was purified by chromatography on silica gel (CH2Cl2/MeOH 98:2→50:50)

Quellen und Nachweise

ORD-Eintrag
ord-f0f48078503b464c9a91efab66fda6ae
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846668B2

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