Synthesis
General procedure for the synthesis of (S)-1-(2-fluorophenyl)ethanol from o-fluoroacetophenone: (R)-methyloxazole borane (0.32 g, 1.2 mmol) was dissolved in tert-butanol (60 mL) under the protection of nitrogen, N,N-diethylanilinoborane (2.6 g, 16 mmol) was added followed by a slow, titrative addition of 1-(2-fluorophenyl)ethanone at 45 °C ( 2.0 g, 14 mmol) in tert-butanol solution (150 mL) and the reaction mixture was stirred. After 1 hour of reaction, the mixture was cooled to room temperature, methanol was added and concentrated. To the concentrate, 1.0 N hydrochloric acid was added and extracted with ethyl acetate, the organic layer was washed with saturated brine and dried with anhydrous sodium sulfate sequentially, and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: hexane to hexane/ethyl acetate=85/15) to afford the title compound (S)-1-(2-fluorophenyl)ethanol (1.9 g, 92% yield) as a colorless liquid.1H-NMR (400 MHz, CDCl3) δ: 1.52 (3H, d, J=6.8 Hz), 5.17-5.24 (1H, m ), 6.98-7.05 (1H, m), 7.15 (1H, ddd, J=1.2, 7.6, 7.6 Hz), 7.21-7.28 (1H, m), 7.49 (1H, ddd, J=1.6, 7.6, 7.6 Hz).
References
[1] Journal of the American Chemical Society, 1998, vol. 120, # 51, p. 13529 - 13530
[2] Tetrahedron: Asymmetry, 2003, vol. 14, # 6, p. 710 - 716
[3] Patent: US2018/162868, 2018, A1. Location in patent: Paragraph 1572-1573
[4] Tetrahedron Asymmetry, 2002, vol. 13, # 13, p. 1347 - 1349
[5] Tetrahedron Letters, 2006, vol. 47, # 27, p. 4619 - 4622
