1,3-Dimethyl-2-imidazolidinone → 5-Bromo-2-methyl-2,3-dihydro-1H-isoindol-1-one

Temperatur

0 °C

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.

1. customA 150 mL sealed tube
2. customThe tube was capped
3. customThis was recooled to 0° C.
4. stirringthis mixture was stirred at room temperature for 4 hours
5. customwas placed in a 150° C.
6. customfor 1 hour
7. washwashed with 1M aqueous HCl
8. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
9. washthe combined organics were washed with water (100 mL) and brine (100 mL)
10. dry with materialdried with MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. customto give a yellow oil
14. customThis was purified by column chromatography
15. washeluting with 1-4% MeOH/DCM

ORD-Eintrag

ord-39882507d4d24cc98189e84ed735ae7e

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08524900B2