Sodium Bicarbonate → Methyl 2-(3-formylphenyl)acetate

m-Tolylacetic acid (50 g) and N-bromosuccimimide (60 g) were refluxed in carbon tetrachloride (400 ml) for 3 h. The mixture was filtered, evaporated in vacuo, and the solid recrystallised from toluene and hexane to give 3-bromomethyl phenylacetic acid (28.6 g) as white needles. δH (250 MHz, DMSO-d6) 3.63 (2H, s, CH2CO), 4.28 (2H, s, CH2Br), 7.1-7.7 (4H, m, ArH). Hydrogen chloride was bubbled through a solution of this acid (25 g) in methanol (500 ml) for 5 min, then the solution stood at room temperature for 1h, evaporated in vacuo, after (300 ml) added, and the solution washed with saturated sodium hydrogencarbonate, water and brine, dried, and evaporated in vacuo to give methyl 3-bromomethylphenylacetate (25 g) as an oil; δH (360 MHz, CDCl3) 3.58 (2H, s, CH2CO), 3.68 (3H, s, Me), 4.47 (2H, s, CH2Br), 7.2-7.4 (4H, m, ArH). The ester (2.5 g) was added to sodium hydrogencarbonate (5 g) in dimethylsulphoxide (35 ml) at 120° C. After 20 min the mixture was cooled in an ice bath, diluted with water and extracted with ether (×3). The ethereal extracts were washed with water and brine, dried, evaporated in vacuo, and purified by flash chromatography eluting with hexane:ethyl acetate (4:1 v/v) to give methyl 3-formylphenylacetate (2.02 g) as an oil; δH (360 MHz, CDCl3) 3.71 (5H, s, CH2 and Me), 7.25-7.4 (2H, m, ArH), 7.8-7.85 (2H, m, ArH), 10.0(1H, s, CHO); m/z (EI+) 178 (M+). Phenyl magnesium bromide (1.9 ml, 3M in ether) was added to a solution of the aldehyde (1.02 g) in ether (20 ml) at-78° C. The mixture was warmed to room temperature, cooled to-78° C. and phenylmagnesium bromide (1.9 ml, 3M) added, then warmed to room temperature. The mixture was washed with saturated ammonium chloride solution, water and brine, dried and evaporated in vacuo to give an oil. Pyridinium chlorochromate (1 g) was added to the oil in dichloromethane (20 ml), and the mixture stirred for 1h. Ether (50 ml) was added, and the mixture filtered through silica gel then evaporated to give an oil (0.63 g). The oil was dissolved in THF (15 ml) and lithium hydroxide (6 ml, 0.5H in water) added. After 1h ether and water were added, the mixture separated, and the aqueous layer acidified with 1N HCl, then extracted with ethyl acetate (×3). The ethyl acetate was washed with water and brine, dried and evaporated in vacuo to give 3-benzoylphenylacetic acid (310mg) as white plates. m.p. 101°-103° C.; δH (250 MHz, CDCl3) 3.76 (2H, s, CH2), 7.4-7.9 (9H, m, ArH); m/z (EI+) 240 (M+). The acid was converted in the standard way to give the title compound as pale yellow plates. m.p. 294°-295° C. (from dimethylformamide/water); (Found: C, 68.94;H, 3.91;N, 3.60. C22H14NO3Cl +0.4 H2O requires C, 68.98;H, 3.89;N, 3.65%); δH (360 MHz, DMSO-d6) 7.31 (1H, dd, J 8.7 and 2.0 Hz, H-6), 7.32(1H, d, J 2.0 Hz, H-8), 7.5-7.9 (9H, m, ArH), 7.96(1H, d, J 8.7 Hz, H-5), 10.6(1H, s, OH), 11.6(1H, s, NH); m/z (EI+) 375 (M+).

1. temperatureAfter 20 min the mixture was cooled in an ice bath
2. extractionextracted with ether (×3)
3. washThe ethereal extracts were washed with water and brine
4. customdried
5. customevaporated in vacuo
6. custompurified by flash chromatography
7. washeluting with hexane:ethyl acetate (4:1 v/v)

ORD record

ord-0e2ade93feca431e91abcd06ddc74a3e

Source dataset

uspto-grants-1996_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05559125