Enantioselective ketone hydrogenation: From R&D to pilot scale with industrially viable Ru/phosphine-oxazoline complexes

被引：45
作者：
Naud, Frederic
Spindler, Felix
Rueggeberg, Carsten J.
Schmidt, Andreas T.
Blaser, Hans-Ulrich
机构：
[1] Solvias AG, Basel, Switzerland
[2] Novasep Synth Switzerland, CH-4133 Pratteln, Switzerland
来源：
ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2007年 / 11卷 / 03期
关键词：
D O I：
10.1021/op0601619
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
The development of a pilot process for the enantioselective hydrogenation of 3,5-bistrifluoromethyl acetophenone (BTMA) using a Ru/phosphine-oxazoline complex in toluene in the presence of aqueous NaOH is described. Various reaction parameters and quality risk factors such as ligand structure, substrate quality, reaction conditions, thermal safety, etc. were investigated. The reaction was carried out twice on a 140-kg scale at 20 bar and 25 degrees C with substrate-to-catalyst ratios of 20,000 with an enantiomeric excess of > 95%. After crystallization, (R)- 3,5-bistrifluoromethyl phenyl ethanol (BTMP) was obtained with an ee between 97.7 and 98.6% in 70% chemical yield.
引用
收藏
页码：519 / 523
页数：5
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