Dibromomethane → HCID 22329508, compound

Temperature

0 °C

To N,N-diisopropylamine (4.06 ml, 2.93 g, 29.0 mmol) in THF (20 ml) was added n-butyllithium (11.6 ml of a 2.5 M solution in hexanes; 29.0 mmol) dropwise, maintaining the temperature of the mixture below 5° C. throughout the addition. The resulting solution was stirred at 0° C. for 15 min, and was then added dropwise to a solution of 2,2-difluoropropionic acid ethyl ester (prepared according to the procedure described in U.S. Pat. No. 5,859,051) (2.00 g, 14.5 mmol) and dibromomethane (2.02 ml, 5.04 g, 29.0 mmol) in THF (20 ml) over 30 min with stirring, maintaining the temperature of the mixture below −60° C. throughout the addition. The solution was stirred for 15 min at −78° C. under nitrogen, and was then quenched by the addition of 5 N hydrochloric acid (10 ml). The mixture was allowed to warm to room temperature, and was diluted with water (10 ml). The aqueous phase was separated and washed with diethyl ether (2×30 ml). The combined organic layers were dried over magnesium sulfate, and concentrated in vacuo. The residual oil was purified by flash chromatography on silica gel, eluting with 10% to 20% diethyl ether in 40-60 petroleum ether (UV detection), yielding 1,1-dibromo-3,3-difluorobutan-2-one as a yellow oil (1.65 g, 43%): 1H NMR (360 MHz, CDCl3) δ 1.90 (3H, t, J 19.2 Hz), 6.39 (1H, s).

1. temperature29.0 mmol) dropwise, maintaining the temperature of the mixture below 5° C.
2. additionthroughout the addition
3. customprepared
4. temperaturemaintaining the temperature of the mixture below −60° C.
5. additionthroughout the addition
6. stirringThe solution was stirred for 15 min at −78° C. under nitrogen
7. customwas then quenched by the addition of 5 N hydrochloric acid (10 ml)
8. temperatureto warm to room temperature
9. additionwas diluted with water (10 ml)
10. customThe aqueous phase was separated
11. washwashed with diethyl ether (2×30 ml)
12. dry with materialThe combined organic layers were dried over magnesium sulfate
13. concentrationconcentrated in vacuo
14. customThe residual oil was purified by flash chromatography on silica gel
15. washeluting with 10% to 20% diethyl ether in 40-60 petroleum ether (UV detection)

ORD record

ord-5b4fef6bef814e3fa64888f0ad0dc7f2

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936608B2