Synthesis
c) Synthesis of (R,S)-6-chloro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid (9c): triethylsilane (2.4 mL, 12.5 mmol) was added slowly and dropwise to a suspension of trifluoroacetic acid (5 mL) of compound 9b (1.13 g, 5 mmol) under stirring. The reaction mixture was stirred continuously at 55°C for three days. Upon completion of the reaction, it was cooled to 25°C and the excess triethylsilane and solvent were removed by distillation under reduced pressure. The residue was dissolved in 1N sodium hydroxide solution and the resulting aqueous solution was washed with ether. Subsequently, the aqueous solution was acidified to pH ~1 with 6N hydrochloric acid and extracted with ethyl acetate. The organic extracts were combined, washed sequentially with water and saturated brine, and dried with anhydrous sodium sulfate. After filtration, the organic phase was concentrated under reduced pressure and finally dried under vacuum to give 0.95 g (90% yield) of the title compound 6-chloro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid.1H NMR (300 MHz, DMSO-d6) δ 13.08 (br s, 1H), 7.15 (m, 2H), 6.86 (d, 1H), 4.83 (t , 1H), 2.82 (m, 1H), 2.76 (m, 1H), 2.11 (m, 2H).
References
[1] Tetrahedron: Asymmetry, 1995, vol. 6, # 4, p. 1001 - 1012
[2] Patent: US2005/54630, 2005, A1. Location in patent: Page/Page column 36
