Reaktion #1341002

Reaktionsgleichung

4-bromo-2-(hydroxymethyl)-N-(2,2,2-trifluoroethyl)benzamide

isopropyl magnesium chloride

bis(dimethylamino)phosphoryl chloride

→

title compound

Ausbeute 88.5%

5-bromo-2-(2,2,2-trifluoroethyl)isoindolin-1-one

Ausbeute 88.5%

Lösungsmittel

tetrahydrofuran

N-methyl-2-pyrrolinone

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeunder 10° C
2. 2
   workup.ADDITIONAfter complete addition, approximately 45 minutes
3. 3
   workup.WAITat room temperature for 60 minutes
4. 4
   Temperaturthe reaction was heated
5. 5
   Temperaturat reflux for 72 hours once the addition
6. 6
   Sonstigethe reaction mixture was carefully quenched with water
7. 7
   ExtraktionThe aqueous was extracted with ethyl acetate (3×100 ml)
8. 8
   Trocknendried over magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated under reduced pressure
11. 11
    Sonstigeto leave a mobile oil which
12. 12
    Sonstigewas purified by column chromatography
13. 13
    Wascheneluting with 20% ethyl acetate/petroleum ether

Vorschrift

To a stirred solution of 4-bromo-2-(hydroxymethyl)-N-(2,2,2-trifluoroethyl)benzamide (3.37 g, 10.8 mmol) in anhydrous tetrahydrofuran (50 ml), N-methyl-2-pyrrolinone (20 mL), cooled to 5° C. under a nitrogen atmosphere was added a solution of 2M isopropyl magnesium chloride in anhydrous THF (25 ml) at such a rate to keep the temperature of the reaction mixture under 10° C. After complete addition, approximately 45 minutes, the reaction mixture was stirred at this temperature for an additional 60 minutes, and then at room temperature for 60 minutes. After that time, the reaction mixture was cooled down to 5° C. and a solution of bis(dimethylamino)phosphoryl chloride (1.85 g, 14.1 mmol) was added dropwise. No exotherm was observed and the reaction was heated at reflux for 72 hours once the addition was complete. After this time no starting material was observed by both TLC and LCMS and the reaction mixture was carefully quenched with water, and acidified with 1M aqueous hydrochloric acid. The aqueous was extracted with ethyl acetate (3×100 ml) and the organic layers were combined and dried over magnesium sulfate, filtered and concentrated under reduced pressure to leave a mobile oil which was purified by column chromatography eluting with 20% ethyl acetate/petroleum ether to afford the title compound as a white solid (2.81 g, 88% yield). 1H NMR (DMSO D6, 400 MHz) 4.36-4.43 (2H, m), 4.62 (2H, s), 7.68-7.74 (2H, m) and 7.93 (1H, s); MS (ES+) 296, (ES−) 292.

Quelle