Sodium hydride → (R)-2-[2-(6-Bromo-3-fluoro-pyridin-2-yl)-2-(2-nitro-benzenesulfonylamino)-propoxy]3,3,3-trifluoro-2-methyl-propionic acid ethyl ester

HRID 538325Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 538325
[CH2:1]([O:3][C:4](=[O:12])[C@:5]([OH:11])([CH3:10])[C:6]([F:9])([F:8])[F:7])[CH3:2].[H-].[Na+].[Br:15][C:16]1[N:21]=[C:20]([C:22]2([CH3:37])[CH2:24][N:23]2[S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[N+:34]([O-:36])=[O:35])(=[O:27])=[O:26])[C:19]([F:38])=[CH:18][CH:17]=1>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:12])[C@:5]([O:11][CH2:37][C:22]([C:20]1[C:19]([F:38])=[CH:18][CH:17]=[C:16]([Br:15])[N:21]=1)([NH:23][S:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N+:34]([O-:36])=[O:35])(=[O:26])=[O:27])[CH3:24])([CH3:10])[C:6]([F:7])([F:8])[F:9])[CH3:2]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 26985621(R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl esterHCID 866680366-Bromo-3-fluoro-2-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine

Produkt 1

HCID 86668035(R)-2-[2-(6-Bromo-3-fluoro-pyridin-2-yl)-2-(2-nitro-benzenesulfonylamino)-propoxy]3,3,3-trifluoro-2-methyl-propionic acid ethyl esterAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of (R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl ester (715 mg, 3.84 mmol) in DMF (4 ml) was added NaH (55%) (154 mg, 3.84 mmol) at room temperature and the reaction mixture was stirred for 30 minutes at room temperature. A solution of 6-bromo-3-fluoro-2-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine (800 mg, 1.922 mmol) in DMF (9 ml) was added and the reaction mixture was stirred at room temperature for hours. The reaction mixture was poured onto a mixture of ice/2N HCl/t-butyl-methylether. The organic layer was washed with sat. sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and evaporated. Silica gel chromatography (cyclohexane/ethyl acetate) afforded the title compound as a mixture of 2 diastereoisomers. 300 mg (26% yield). TLC (cyclohexane/ethyl acetate 2:1) Rf=0.42; LCMS RtH5=1.25 min (100%, TIC ES+602, 604).

Aufarbeitung

  1. stirringthe reaction mixture was stirred at room temperature for hours
  2. washThe organic layer was washed with sat. sodium bicarbonate solution and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-59d3be46eaad4fdf983ce917d839a2a7
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865712B2

Notizen zur Reaktion

Wird geladen…