Yield:84109-21-7 87%

Reaction Conditions:

Stage #1: 4-bromo-2-chlorophenolwith sodium hydride in N,N-dimethyl-formamide at 0; for 0.75 h;Inert atmosphere;
Stage #2: allyl bromide in N,N-dimethyl-formamide at 0 - 20;Concentration;Time;

Steps:

21.1

A solution of 4-bromo-2- chlorophenol (10.0 g, 48.0 mmol) in anhydrous DMF (30 mL) was added to a stirred suspension of sodium hydride (2.31 g, 58.0 mmol) in DMF (20 mL) cooled to OoC under nitrogen over 15 min, and stirring continued for 30 min. 3-Bromoprop-l-ene (7.00 g, 58.0 mmol) was added dropwise at 0 oC. After 1 h, the mixture was allowed to warm to room temperature and then stirred for 3 d. Aqueous saturated NH4C1 (50 mL) was added over 10 min with ice-cooling, and the mixture was concentrated. The residue was treated with water (100 mL) and the mixture extracted with ethyl acetate (3 x 120 mL). The combined, dried (Na2S04) organic extracts were concentrated to give an oil which contained DMF. A solution of the oil in ethyl acetate (100 mL) was washed with water (100 mL) and the dried (Na2S04) organic layer was concentrated to give the desired compound (11.6 g, 87% yield) as a colourless oil. ?? (500 MHz, CDC13) 7.50 (d, J = 2.40 Hz, 1H), 7.30 (dd, J = 2.40, 8.77 Hz, 1H), 6.79 (d, J = 8.78 Hz, 1H), 6.04 (ddt, J = 5.10, 10.38, 17.14 Hz, 1H), 5.45 (dd, J = 1.44, 17.26 Hz, 1H), 5.32 (dd, J = 1.33, 10.57 Hz, 1H), 4.59 (d, J = 5.10 Hz, 2H).

References:

WO2013/33085,2013,A1 Location in patent:Paragraph 00259