N,N,N',N'-Tetramethylethylenediamine → 2-Bromo-6-methoxy-4-(trifluoromethyl)benzoic acid

温度

-75 °C

To −75° C. cooled THF (70 ml) was added dropwise 36 ml (50.0 mmol) of a 1.4 M sec-BuLi solution in cyclohexane within 5 minutes keeping the temperature below −70° C. 7.5 ml (50.0 mmol) TMEDA were added dropwise at temperature below −70° C. within 5 minutes. A solution of 5.0 g (22.71 mmol) 2-methoxy-4-(trifluoromethyl)benzoic acid (commercial) in THF (25 ml) was added dropwise at over a period of 20 minutes. The dark green solution was stirred at −75° C. for 2 hours. A solution of 29.6 g (90.84 mmol) 1,2-dibromotetrachloroethane in THF (30 ml) was added dropwise. The off-white suspension was stirred at −75° C. for 1 hour and then allowed to warm to room temperature. The yellow solution was quenched by dropwise addition of 60 ml water under ice bath cooling. The mixture was diluted with ethyl acetate (70 ml) and water (30 ml). The aqueous layer was extracted with ethyl acetate (50 ml), acidified with HCl 25% and extracted with ethyl acetate (3×50 ml). The extracts were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was stirred in heptane, filtered and dried. The solid was recrystallized from heptane (7 ml) and ethyl acetate (2 ml) to provide 815 mg (12%) of the title compound as a white solid. MS (m/e): 298.9 (M−H).

1. customthe temperature below −70° C
2. stirringThe off-white suspension was stirred at −75° C. for 1 hour
3. temperatureto warm to room temperature
4. customThe yellow solution was quenched by dropwise addition of 60 ml water under ice bath
5. temperaturecooling
6. additionThe mixture was diluted with ethyl acetate (70 ml) and water (30 ml)
7. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
8. extractionextracted with ethyl acetate (3×50 ml)
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. stirringThe crude product was stirred in heptane
13. filtrationfiltered
14. customdried
15. customThe solid was recrystallized from heptane (7 ml) and ethyl acetate (2 ml)

ORDレコード

ord-b76ff44ac251496d8d6332b323985024

出典データセット

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08080541B2