Diisopropylamine → 1-(5-Bromo-2-fluorophenyl)ethanone

Temperatur

-70 °C

A solution of 17.78 ml (126 mmol) diisopropyl amine in 375 ml THF was cooled to −78° C. A 1.6 M solution of BuLi in hexanes (79 ml, 126 mmol) was added drop wise. After 15 minutes 20 g of 4-bromo-1-fluoro benzene (114 mmol) was added dropwise while keeping the temperature below −60° C. After stirring for 2.5 h at −70° C. 13.22 ml ethyl difluoro acetate were added. The mixture was warmed to −40° C. and then quenched by pouring the mixture onto 1M HCl. The mixture was extracted with ligroine, dried with MgSO4.H2O, concentrated and purified by column chromatography (silica gel; hexane/5-15% TBME) to give the desired product as a yellow liquid. 1H-NMR (CDCl3, 360 MHz): 8.09 (dd, 1H), 7.82-7.77 (m, 1H), 7.17 (t, 1H), 6.45 (t, 1H, CHF2)

1. customthe temperature below −60° C
2. temperatureThe mixture was warmed to −40° C.
3. customquenched
4. additionby pouring the mixture onto 1M HCl
5. extractionThe mixture was extracted with ligroine
6. dry with materialdried with MgSO4.H2O
7. concentrationconcentrated
8. custompurified by column chromatography (silica gel; hexane/5-15% TBME)

ORD-Eintrag

ord-7b551148282c46dabae0aa0aae5dc79b

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08846658B2