反应详情

温度

2 °C

A solution of iodine (2.25 g) in tetrahydrofuran (6 ml) was added dropwise to a stirred slurry of zinc (Britannia Alloys) (3.00 g) and lead (0.15 g) in tetrahydrofuran (19 ml) under a nitrogen atmosphere at 25° C. The reaction temperature was allowed to rise during the addition. The mixture was then cooled to 2° C. A solution of 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (2.00 g), 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine (see Preparation 1) (2.84 g) and iodine (0.02 g) in tetrahydrofuran (16 ml) was added dropwise over 10 minutes. The reaction temperature was limited to a maximum of 16° C. during the addition by cooling. Further cooling was then applied to obtain a temperature below +5° C. The reaction was stirred below +5° C. for 30 minutes. A sample of the reaction mixture was taken and subjected to HPLC analysis according to the conditions set out in Example 1. The analysis showed a 10.3:1 molar ratio of the 2R,3S/2S,3R to the 2R,3R/2S,3S enantiomeric pair of the title compound. The yield of the 2R,3S/2S,3R enantiomeric pair was calculated to be 90% using an internal standard.

1. additionto rise during the addition
2. additionThe reaction temperature was limited to a maximum of 16° C. during the addition
3. temperatureby cooling
4. temperatureFurther cooling
5. customto obtain a temperature below +5° C