Ethyl 2-acetoxy-5-broMobenzoate synthesis

Yield:1131622-49-5 98%

Reaction Conditions:

with triethylamine;dmap at 20; for 24 h;

Steps:

7

In a 50 ml. round-bottomed flask fitted with condenser and magnetic stirrer were placed methyl 5-bromosalicylate (5.0 g, 21.64 mmol) , AC₂O (2.65 g, 25.97 mmol), Et₃N (2.63 g, 25.97 mmol) and catalytic amount of DMAP. The reaction mixture was stirred for 24 h at rt. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was washed with water, dried and concentrated to give the acetoxy derivative (5.9 g, 98%). To a stirred solution of methyl 2-acetoxy-5-bromobenzoate (5.9 g, 21.61 mmol) in acetonitrile (80 ml_) were added 4-acetoxystyrene (3.68 g, 22.69 mmol), N₁N- diisopropylethylamine (8.38 g, 64.82 mmol), biphenyl-2-yl-di-t-butyl phosphine (368 mg, 1.29 mmol) and palladium acetate (291 mg, 1.29 mmol) under N₂. The reaction mixture was heated to 80 °C for 48 h and then cooled to rt. Water was added and the mixture was extracted with EtOAc. The organic layer was separated, washed with water, brine, dried and concentrated to give crude EPO product, which was purified by column chromatography, using 20% EtOAc in hexane to give (3.19 g, 42%) of the di-acetoxy stillbene. The di-acetoxystillbene (500 mg, 1.41 mmol) was treated with ammonia (2M solution in ethanol, 15 ml_) in a sealed tube at 115 ⁰C for 12 h. The reaction mixture was cooled to rt. The solvent was removed and the crude product was purified by column chromatography using 50% EtOAc in hexane to give the product (200 mg, 50%).MS (ES) m/z: 284.12 (M), 283.14 (M-1 ); ¹³C-NMR (DMSO-d₆): δ 169.5, 159.9,157.8, 133.2, 130.4, 129.9, 128.8, 128.4, 128.3, 127.8, 124.5, 118.6, 116.2, 115.9,113.9, 62.1 , 14.7; Mp. 269-271 °C.

References:

WO2006/45010,2006,A2 Location in patent:Page/Page column 162-163