Central Glass Company, Limited

Tokyo Institute of Technology

Kaori Mogi

Akihiro Ishii

Manabu Yasumoto

Takashi Ootsuka

Kenjin Inomiya

Hideyuki Tsuruta

Koji Ueda

Takako Yamazaki

Takashi Masuda

Koichi Mikami

Kazunori Mori

Kohsuke Aikawa

Akihiro Ishi

An &#x3b1;-trifluoromethyl-&#x3b1;,&#x3b2;-unsaturated ester can be produced by reacting an &#x3b1;-trifluoromethyl-&#x3b1;-hydroxy ester with sulfuryl fluoride (SOF) in the presence of an organic base. It is preferable that the raw substrate has a hydrogen atom as one &#x3b2;-position substituent group and either an alkyl group, a substituted alkyl group, an alkenyl group, a substituted alkenyl group, an aromatic ring group or a substituted aromatic ring group as the other &#x3b2;-position substituent group. It is more preferable that an ester moiety of the raw substrate is an alkyl ester. This raw substrate is readily available. Further, the desired reaction can proceed favorably with the use of this raw substrate. It is also preferable to use either 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the organic base. The desired reaction can proceed more favorably with the use of this organic base.

Process for producing &#x3b1;-trifluoromethyl-&#x3b1;,&#x3b2;-unsaturated ester

&#x3b1;-Trifluoromethyl-&#x3b2;-substituted-&#x3b2;-amino acids can be produced by allowing &#x3b1;-trifluoromethyl-&#x3b2;-substituted-&#x3b1;,&#x3b2;-unsaturated esters to react with hydroxylamine to convert &#x3b1;-trifluoromethyl-&#x3b2;-substituted-&#x3b1;,&#x3b2;-unsaturated esters into dehydrogenated closed-ring body of &#x3b1;-trifluoromethyl-&#x3b2;-substituted-&#x3b2;-amino acid, and by hydrogenolyzing the dehydrogenated closed-ring body. According to this production process, novel &#x3b1;-trifluoromethyl-&#x3b2;-substituted-&#x3b2;-amino acids which are free amino acids whose functional groups are not protected can be produced, in which &#x3b2;-position substituent is not limited to aromatic ring group or substituted aromatic ring group while the relative stereochemistry of &#x3b1;-position and &#x3b2;-position can be also controlled.

Process for production of &#x3b1;-trifluoromethyl-&#x3b2;-substituted-&#x3b2;-amino acid

An optically active, fluorine-containing carbonyl-ene product is produced by reacting a fluorine-containing &#x3b1;-ketoester with an alkene in the presence of a transition metal complex having an optically active ligand. There are Mode 1 of conducting this reaction in the absence of reaction solvent, Mode 2 of conducting this reaction in a solvent that is low in relative dielectric constant, and Mode 3 of conducting this reaction in a halogenated hydrocarbon-series solvent. In each of these three modes, it is possible to produce the optically active, fluorine-containing carbonyl-ene product with low cost.

Method for producing optically active fluorine-containing carbonyl-ene product

There is provided a novel, useful dehydroxyfluorination agent containing sulfuryl fluoride (SOF) and an organic base that is free from a free hydroxyl group in the molecule. According to the present dehydroxyfluorination agent, it is not necessary to use perfluoroalkanesulfonyl fluoride, which is not preferable in large-scale use, and it is possible to advantageously produce optically-active fluoro derivatives, which are important intermediates of medicines, agricultural chemicals and optical materials, for example, 4-fluoroproline derivatives, 2'-deoxy-2&#x2032;-fluorouridine derivatives, optically-active &#x3b1;-fluorocarboxylate derivatives, and monofluoromethyl derivatives, even in large scale.

Dehydroxyfluorination agent

There is provided a method for producing an optically active 1-(fluoro-, trifluoromethyl- or trifluoromethoxy-substituted phenyl)alkylamine N-monoalkyl derivative, which includes the steps of conducting reductive alkylation of an optically active secondary amine and a formaldehyde (including an equivalent thereof) or lower aldehyde in the presence of a transition metal catalyst under a hydrogen gas atmosphere, thereby converting the secondary amine to an optically active tertiary amine of the formula, and subjecting the tertiary amine to hydrogenolysis. The target optically active compound can be produced efficiently by this production method.

Method for producing optically active 1-(fluoro-, trifluoromethyl- or trifluoromethoxy-substituted phenyl) alkylamine N-monoalkyl derivative

It was found that a fluoro derivative can be produced by reacting a hydroxy derivative with sulfuryl fluoride (SOF) in the presence of an organic base or in the presence of an organic base and 'a salt or complex comprising an organic base and hydrogen fluoride'. According to the present production process, it is not necessary to use perfluoroalkanesulfonyl fluoride, which is not preferable in industrial use, and it is possible to advantageously produce optically-active fluoro derivatives, which are important intermediates of medicines, agricultural chemicals and optical materials, specifically 4-fluoroproline derivatives, 2'-deoxy-2&#x2032;-fluorouridine derivatives, optically-active &#x3b1;-fluorocarboxylate derivatives, and the like, even in a large scale.

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Fujimino, Japan

Kaori Mogi