Uses

Reactant involved in synthesis of:

• Aroylbenzoxepinones for analgesic activity
• (Heteroaryl)(carboxamido)arylpyrrole derivatives with Cdc7 kinase inhibitory activity
• Cambinol analogs for sirtuin inhibition and antitumor activity
• TunePhos-type diphosphine ligands via asymmetric hydrogenation

Synthesis

24398-88-7

141-78-6

21575-91-7

A solution of 1.3 M LHMDS (25 mL, 32.7 mmol) in THF (10 mL) was stirred at -78 °C and under an inert atmosphere, and ethyl acetate (1.9 g, 21.8 mmol) was added slowly. After stirring for 15 min, ethyl 3-bromobenzoate (5 g, 21.8 mmol) was added and stirring was continued for 2 hours. The reaction progress was monitored by TLC. Upon completion of the reaction, the reaction was quenched with 10 mL of saturated aqueous NH4Cl and extracted with ethyl acetate (3 x 20 mL). The organic phases were combined, dried with anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography with 4% ethyl acetate/hexane as eluent to afford the target compound, ethyl 3-bromobenzoylacetate (4.5 g, 76.9%) as a mixture of enol forms in the form of a brown oil.1H NMR (500 MHz, CDCl3): δ 8.07 (s, 1H), 7.86 (d, J=7.5 Hz, 1H), 7.73 -7.69 (m, 1H), 7.37 (t, J=7.0Hz, 1H), 4.28-4.26 (m, 2H), 3.92 (s, 2H), 1.24 (t, J=6.2Hz, 3H).MS (ESI): m/z 298.8 [M-1].

References

[1] Patent: WO2015/191630, 2015, A1. Location in patent: Paragraph 00457
[2] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 13, p. 2991 - 3013