Synthesis
(S)-3-Benzoylamino tetrahydrofuran (20.0 g, 0.105 mol) was dissolved in ethanol (40 mL), followed by addition of an aqueous sodium hydroxide solution (25 g sodium hydroxide dissolved in 120 mL of water). The reaction mixture was heated to reflux for 9-10 h. The reaction was monitored by TLC until complete disappearance of the starting material. After completion of the reaction, the mixture was cooled to room temperature and acidified with dilute hydrochloric acid. The precipitated benzoic acid was removed by filtration and the aqueous phase was washed with dichloromethane and concentrated to give a crude product containing the salt. Isopropanol was added to the crude product and stirred at room temperature for 1 hour. The salt was removed by filtration and the filtrate was concentrated to dryness to give a paste. The paste was co-stirred with isopropanol to promote crystallization and subsequently filtered, washed with cold isopropanol and dried under vacuum. Yield: 11 g (85% of theoretical yield); Melting point: 165-170 °C; [α]27D = -10.2 (c 1 , methanol); 1H NMR (300 MHz, CDCl3) δ (ppm): 3.80-4.11 (m, 5H), 2.37-2.5 (m, 1H), 2.01-2.09 (m, 1H); 13C NMR ( 300 MHz, CDCl3) δ (ppm): 70.49, 66.82, 51.21, 30.01; Elemental analysis (C4H10ClNO, FW 123.5813) Calculated values: C, 38.88; H, 8.16; N, 11.33. Measured values: C, 38.97; H, 7.86; N, 11.39. By transforming the product converted to its benzoyl derivative and analyzed by chiral HPLC using a Chiralpak AD-H column to determine the enantiomeric excess (Figure 2).
References
[1] Tetrahedron Asymmetry, 2013, vol. 24, # 11, p. 663 - 668
[2] Patent: US2008/255377, 2008, A1. Location in patent: Page/Page column 3
