H-GAMMA-ABU-OBZL P-TOSYLATE

Synthesis

A suspension of γ-aminobutyric acid (GABA) (3.50 g, 0.034 mol), benzyl alcohol (7.30 g, 7 mL, 0.068 mol), and p-toluenesulfonic acid monohydrate (PTSA) (7.10 g, 0.037 mol) was heated to reflux for 5 hr in toluene (200 mL), and the resulting water was removed by azeotropic distillation. Upon completion of the reaction, the mixture was concentrated to one-third of the original volume and the product was subsequently precipitated by the addition of ether (100 mL). The precipitate was collected by filtration, dissolved in methanol (60 mL) and reprecipitated by adding ether (100 mL) again. After filtration, it was dried to obtain 4-methylbenzenesulfonate, 4-aminobutyric acid benzyl ester (12.30 g, 99% yield) in the form of white crystals. The melting point of the product was 106.2-106.7 °C (determined in ether); Infrared spectrum (ATR): 3100, 3039, 2942, 1732, 1642, 1532, 1188, 1125 cm^-1; ^1H NMR (200 MHz, CD3OD): δ = 7.71 (d, J = 8.0 Hz, 2H, HPTSA), and 7.37-7.30 (m, 5H, HCAr), 7.20 (d, J=8.4 Hz, 2H, HPTSA), 5.11 (s, 2H, H2CBn), 2.95 (t, J=7.5 Hz, 2H, H2C(4)GABA), 2.47 (t, J=7.3 Hz, 2H, H2C(2)GABA), 2.33 (s 3H, H3CPTSA), 1.92 (quint, J=7.4 Hz, 2H, H2C(3)GABA) ppm; ^13C NMR (50 MHz, CD3OD): δ=173.83 (CO2Bn), 143.35, 141.82, 137.43, 129.91, 129.59, 129.30, 126.91 (CAr), 67.44 (CH2Bn), 40.00 (CH2(4)GABA), 31.59 (CH2(2)GABA), 23.65 (CH2(3)GABA), 21.30 (CH3PTSA) ppm; Mass Spectra (ESI): calculated values of C11H16NO2 ([M+H]+): 194.1181, measured value: 194.1167.

References

[1] Tetrahedron, 2017, vol. 73, # 50, p. 7073 - 7078
[2] Organic and Biomolecular Chemistry, 2009, vol. 7, # 11, p. 2327 - 2337
[3] RSC Advances, 2015, vol. 5, # 81, p. 66339 - 66354
[4] Patent: WO2014/59158, 2014, A1. Location in patent: Page/Page column 38-39
[5] Tetrahedron Letters, 2015, vol. 56, # 48, p. 6803 - 6806