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Entry
Acyl Donor (1 eq) 1 2 3
Conv. (%)
Isopropenyl acetate Ethyl acetate Vinyl acetate
e.e.prod (%)
44
99 32 26
E
>200 99 >200 95 54
Reaction conditions: 1-(2,6-dichloro-3-fluorophenyl)-ethanol (2) (0.048 mmol, 10mg), isopropenyl acetate or vinyl acetate or ethyl acetate (1eqv) as acyl donor, and 60mg (20%w/v) of CAL B Novozym 435 (N435) in cyclohexane (3 mL) for 10 days at 60 °C, measured by GC-FID method and enantioselectivity was measured based on (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol and the corresponding ester retention times.
4.Approvals and indications for Crizotinib powder On August 26, 2011, the U.S. Food and Drug Administration approved Crizotinib powder (Xalkori) to treat certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. Approval required a companion molecular test for the EML4-ALK fusion. In March 2016, the U.S. Food and Drug Administration approved Crizotinib powder in ROS1-positive non-small cell lung cancer. As expected, isopropenyl acetate lead to the best results on the kinetic resolution of 1-(2,6-dichloro-3-fluorophenyl)ethanol (2), arriving on the desired acetylated R-enantiomer in good conversions and high selectivity (Table 1, entry 1). Vinyl acetate was probably too reactive under the designed reaction conditions, leading to a decrease of enantiomeric ratio. A blank experiment was performed in order to evaluate the uncatalyzed reaction and small amounts of acetylated alcohol could be obtained (<10%). Regarding ethyl acetate, surprisingly, it presented interesting selectivity with moderate conversion (Table 1, entries 3 and 2 respectively). Despite the fact that Table 1 present the results for the kinetic resolution after 10 days, the reactions were monitored in the first 3 days every 12 h and after the 3rd day, every 24 h. What could be seen is the conversion 6
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