Uses
4,7-Dihydro-2,2-dimethyl-1,3-dioxepin is an intermediate in the synthesis of Calcobutrol (C145700), a new macrocyclic polyhydroxylated gadolinium chelate derivative which can be used as a contrast agent for Magnetic Resonance Imaging (MRI).
Synthesis
GENERAL STEPS: cis-1,2-dihydroxymethylene (9.3 mL, 113 mmol) was dissolved in dichloromethane (DCM) under argon protection, p-toluenesulfonic acid monohydrate (p-TSA-H2O, 1.08 g, 6.2 mmol) was added at room temperature, followed by dropwise addition of 2,2-dimethoxypropane (27.9 mL, 227 mmol). The reaction mixture was stirred at room temperature for 3 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium bicarbonate (NaHCO3) (50 mL) and extracted with dichloromethane (2 x 50 mL). The organic layers were combined, washed with brine (25 mL) and dried over anhydrous magnesium sulfate (MgSO4). The solvent was slowly evaporated under reduced pressure to afford the colorless oily product 4,7-dihydro-2,2-dimethyl-1,3-dioxepin (10.5 g, 72% yield). The crude product could be used for subsequent reactions without further purification. Thin layer chromatography (TLC) analysis showed an Rf value of 0.51 (ethyl acetate/hexane, 20%). Nuclear magnetic resonance hydrogen spectra (1H NMR, 400 MHz, CDCl3) showed δ 5.66 (2H, triple peak, J = 1.6 Hz, H-1), 4.25 (4H, double peak, J = 1.6 Hz, H-2), and 1.43 (6H, single peak, H-4) ppm. nuclear magnetic resonance carbon spectra (13C NMR, 101 MHz, CDCl3) showed δ 129.5 (2C, C-1), 102.0 (1C, C-3), 61.4 (2C, C-2), 24.0 (2C, C-4) ppm. the obtained data are in agreement with literature reports.
References
[1] Helvetica Chimica Acta, 2000, vol. 83, # 7, p. 1633 - 1644
[2] Tetrahedron Asymmetry, 1995, vol. 6, # 6, p. 1261 - 1272
[3] Patent: US5962704, 1999, A
[4] Patent: US6133461, 2000, A
[5] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 2883 - 2887
