Reaktion #68501

Reaktionsgleichung

4-bromo-2-(hydroxymethyl)-N-methylbenzamide

1,3-dimethylimidazolidin-2-one

Isopropylmagnesium chloride

→

5-bromo-2-methylisoindolin-1-one

Ausbeute 57.3%

Lösungsmittel

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 150 mL sealed tube
2. 2
   SonstigeThe tube was capped
3. 3
   SonstigeThis was recooled to 0° C.
4. 4
   workup.STIRRINGthis mixture was stirred at room temperature for 4 hours
5. 5
   Sonstigewas placed in a 150° C.
6. 6
   Sonstigefor 1 hour
7. 7
   Waschenwashed with 1M aqueous HCl
8. 8
   ExtraktionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
9. 9
   Waschenthe combined organics were washed with water (100 mL) and brine (100 mL)
10. 10
    Trocknendried with MgSO4
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated
13. 13
    Sonstigeto give a yellow oil
14. 14
    SonstigeThis was purified by column chromatography
15. 15
    Wascheneluting with 1-4% MeOH/DCM

Vorschrift

A 150 mL sealed tube was charged with 4-bromo-2-(hydroxymethyl)-N-methylbenzamide (3.34 g, 13.7 mmol) and 1,3-dimethylimidazolidin-2-one (40.4 ml, 369 mmol). The solution was cooled to 0° C. and Isopropylmagnesium chloride (15.3 ml, 30.5 mmol) was added slowly. The tube was capped and the reaction mixture was stirred at room temperature for 30 minutes. This was recooled to 0° C. and N,N,N,N-tetramethylphosphorodiamidoyl chloride (2.64 ml, 17.8 mmol) was added in one portion; this mixture was stirred at room temperature for 4 hours. The tube was placed in a 150° C. oil bath for 1 hour. The mixture was then diluted with EtOAc (100 mL), then washed with 1M aqueous HCl. The aqueous layer was extracted with ethyl acetate (3×100 mL) and then the combined organics were washed with water (100 mL) and brine (100 mL), dried with MgSO4, filtered, then concentrated to give a yellow oil. This was purified by column chromatography, eluting with 1-4% MeOH/DCM to give 5-bromo-2-methylisoindolin-1-one (1.774 g, 57.3% yield) as a yellow solid.

Quelle