A facile 7-step procedure for the synthesis of enantiomerically pure 1-（5-bromo-2-chlorophenyl）-1-（4-ethoxyphenyl）ethanes[（R）-2 and（S）-2] that started from （5-bromo-2-chlorophenyl）（4-ethoxyphenyl）methanone 3 was developed.The key step was the resolution of 2-（5-bromo-2-chlorophenyl）-2-（4-ethoxyphenyl）acetic acid 6 by crystallizations of its L-and D-menthyl esters 7 and 8 from petroleum ether to give optically pure enantiomers 9 and 10,respectively.The absolute configurations of the products were unambiguously determined by single-crystal X-ray diffractions of four key intermediates,9,10,13 and 14.This procedure is characterized by inexpensiveness,scalability and ability to produce two individual enantiomers of a diarylethane with unambiguously determined absolute configurations and high enantiomeric purities.
The title compound tianagliflozin triacetate 1 was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic system （C27H31C108, Mr = 518.97）, space group P21 with a = 5.3913（11）, b = 16.137（2）, c = 15.411（3） A, β = 94.15（3）°, V = 1337.3（5） A3, Z = 2, Dc = 1.289 g/cm3, F（000） = 548,μ = 0.190 mm1, the final R = 0.0374 and wR = 0.0809 for 3981 observed reflections （I 〉 2σ（I））. The structure of 1, triacetate of a highly potent SGLT2 inhibitor tianagliflozin, was unambiguously determined by single-crystal X-ray diffraction, which helped to confirm the desired fl configuration at the anomeric center and the position where the deoxylation occurred. The two benzene rings in the lattice are basically orthogonal to each other. There are four intermolecular hydrogen bonds in the crystal, which helps to further stabilize the crystal.
