Diethyl-1,1,1',1'-D4-stilbestrol-3,3',5,5'-D4 (Hexestrol-D8) was prepared as follows: hexestrol (1.0 g) was dissolved in a mixture of 15 g methanol-d4 and 6 g deuterium chloride. The mixture was heated in a closed vessel at 85C for three days. After cooling the solution to room temperature, the mixture was concentrated and dried under vacuum. The exchange reaction was then repeated twice under the same conditions with the same amount of deuterated reagent. After the third exchange reaction, an aliquot of the mixture was dried, trimethylsilylated and analyzed by GC-MS. Isolation of the product of the isotope enrichment reaction. Dimethyl sulfoxide (8 ml) was added to the dried reaction product and the mixture was heated on a steam bath for 3 min. The contents were diluted with water (16 ml) and filtered immediately. The collected precipitate was dissolved in ether and the organic phase was washed twice with water. The organic phase was concentrated in vacuum and the residue was dried and recrystallized to give hexestrol-D8.
