Methyl 6-((4-bromo-2-chlorophenyl)amino)-7-fluoro-1H-benzo[d]imidazole-5-carboxylate → [6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-methanol

Temperature

-78 °C

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 8b (1.06 g, 2.65 mmol) is suspended in tetrahydrofuran (25 mL) and cooled to −78° C. Lithium aluminum hydride (8.03 mL, 8.03 mmol, 1M solution in tetrahydrofuran) is added dropwise to the reaction mixture. After stirring for 10 minutes at −78° C., the reaction mixture is warmed to 0° C. and becomes a homogeneous solution. The reaction mixture is stirred for 5 minutes at 0° C. and then cooled again to −78° C. The reaction mixture is quenched with MeOH, diluted with Rochelle's salt, warmed to room temperature and stirred for 1 hour. The reaction mixture is then poured into a separatory funnel, diluted with ethyl acetate, and the layers separated. The aqueous phase is extracted with ethyl acetate. The combined ethyl acetate layers are dried (Na2SO4) and concentrated under reduced pressure to yield 0.98 g (100%) of the pure desired product as a pale yellow solid. MS ESI (+) m/z 370, 372 (M+, Br pattern) detected.

1. temperaturethe reaction mixture is warmed to 0° C.
2. stirringThe reaction mixture is stirred for 5 minutes at 0° C.
3. temperaturecooled again to −78° C
4. customThe reaction mixture is quenched with MeOH
5. additiondiluted with Rochelle's salt
6. temperaturewarmed to room temperature
7. stirringstirred for 1 hour
8. additionThe reaction mixture is then poured into a separatory funnel
9. additiondiluted with ethyl acetate
10. customthe layers separated
11. extractionThe aqueous phase is extracted with ethyl acetate
12. dry with materialThe combined ethyl acetate layers are dried (Na2SO4)
13. concentrationconcentrated under reduced pressure

ORD record

ord-40f1000fcf1f40d0a044e82b365b37f9

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07973170B2