99109-07-6

Usage

Uses

An impurity of Diltiazem (D460620).

Upstream product

• 105560-93-8 methyl (2R,3S)-3-(4-methoxyphenyl)glycidate 
• 137-07-5 2-amino-benzenethiol 
• 96125-49-4 methyl trans-3-(4-methoxyphenyl)glycidate 
• 4875-10-9 o-nitrothiophenol 
• 42245-42-1 methyl (2-RS,3-SR)-2,3-epoxy-3-(4-methoxyphenyl)propanoate 
• 123-11-5 4-methoxy-benzaldehyde 
• 30067-00-6 (2RS,3SR)-2-hydroxy-3-(4-methoxy-phenyl)-3-(2-nitro-phenylsulfanyl)-propionic acid methyl ester 
• 126060-70-6 (2R,3R)-3-(4-Methoxy-phenyl)-oxirane-2-carboxylic acid methyl ester 
• 127347-52-8 (2S,3R)-3-Hydroxy-3-(4-methoxy-phenyl)-2-(2,4,6-trichloro-benzenesulfonyloxy)-propionic acid methyl ester 
• 122517-80-0 (2S,3R)-(-)-methyl 2,3-dihydroxy-3-(p-methoxyphenyl)propionate 
• 125354-93-0 (2S,3S) methyl 2-hydroxy-3-(4-methoxyphenyl)-3-(2-nitrophenylthio)propionate 

Downstream Products

• 42399-49-5 (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one 
• 42399-41-7 diltiazem 
• 27068-88-8 3c-hydroxy-2r-(4-methoxy-phenyl)-2,3-dihydro-5H-benzo[b][1,4]thiazepin-4-one 
• 42399-53-1 (2RS,3RS)-cis-2,3-dihydro-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one 
• 23515-44-8 5-(2-dimethylamino-ethyl)-3c-hydroxy-2r-(4-methoxy-phenyl)-2,3-dihydro-5H-benzo[b][1,4]thiazepin-4-one 
• 42399-40-6 O-desacetyldiltiazem 
• 42399-48-4 (2S,3S)-threo-2-hydroxy-3-(2-aminophenylthio)-3-(4-methoxyphenyl)-propionic acid 

Relevant academic research and scientific papers

Enantioselectivity of Pseudomonas cepacia lipase for the acetylation of 2-hydroxy carboxylic acid esters+

Structurally different ethyl or methyl 2-hydroxy carboxylates were resolved by Pseudomonas cepacia lipase-catalysed acetylations with vinyl acetate in diethylether. One type of the alcoholic substrates (2-hydroxy-2-arylacetates and 2-hydroxy-3-arylpropinates) contained a HO-group at the stereocentre. These compounds were resolved with high enantioselectivity (ee 91 → 99) at ca. 50% conversion. The other alcoholic substrates ((threo-2-hydroxy-3-methylbutyrate and threo- or erythro-2-hydroxy-3-aryl-3-arylthio(or aryloxy)propionates) with two stereocentres generally resulted in enantiopure products and the reactions stopped at 50 % conversion.

Optical resolution of a 1,5-benzothiazepine derivative, a synthetic intermediate of diltiazem, by preferential crystallization and diastereomeric salt formation

Practical preparation methods of an optically active intermediate of diltiazem, (+)-(2S,3S)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2- (4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one [(+)-7], have been developed by the use of physicochemical and chemical resolutions. 1) The salt of (+)-7 with 3-amino-4-hydroxy-benzenesulfonic acid (AHS), was found to exist as a conglomerate and could be reproducibly resolved into (+)-7·AHS and (-)- 7·AHS of 94-98% ee by a preferential crystallization procedure. 2) (+)- (1R)-3-Bromocamphor-9-sulfonic acid [(+)-BCS] was found to be an efficient resolving agent for (±)-7 and the diastereomeric resolution provided (+)- 7·(+)-BCS·2H2O salt in >43% yield and >97% ee by fractional crystallization. It is presumed that the crystal water of (+)-7·(+)- BCS·2H2O plays an important role in the selective crystallization during this efficient resolution.

Process for preparing 1,5-benzothiazepine derivatives

There is disclosed a process for preparing 1,5-benzothiazepine derivatives of the formula: STR1 wherein R1 is a lower alkyl group, or a salt thereof which comprises subjecting a propionate derivatives of the formula: STR2 wherein R2 is an ester residue and R1 is the same as defined above, to intramolecular cyclization in the presence of a sulfonic acid compound of the formula: wherein R3 is a lower alkyl group or a substituted or unsubstituted phenyl group, in a non-halogenated organic solvent and, if desired, converting the product to a salt thereof.

Process for the resolution of intermediates useful in the preparation of 1,5-benzothiazepines

A process for the resolution of amminoesters of the formula STR1 wherein R1 and R3 have the meanings reported in the specification, by tartaric acid and analogs thereof, is described. The compounds of formula IV-A are intermediates useful in the preparation of optically active (2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)ones.

2-Hydroxy-propanoic acid acyclic alkyl esters for benzothiazepines

In general, the present invention provides, in one aspect, a process comprising contacting a 2-Aminothiophenol with an optically active 3-(4-alkyloxyphenyl)glycidic acid acyclic alkyl ester by step(s) under conditions such that an optically active 2-hydroxy-3-(4-alkyloxyphenyl)-3-(2-Aminophenylthio)propionic acid acyclic alkyl ester is prepared. Another aspect comprises the optically active 2-hydroxy-3-(4-alkyloxyphenyl)-3-(2-Aminophenylthio)propionic acid acyclic alkyl ester. A preferred aspect is a process comprising contacting 2-aminothiophenol per se with a 3-(4-methoxyphenyl)glycidic acid methyl ester by step(s) under conditions such that a 2-hydroxy-3-(4-methoxyphenyl)-3-(2-aminophenylthio)propionic acid methyl ester is prepared.

Asymmetric syntheses of (+)-diltiazem hydrochloride

Efficient enantioselective syntheses of the important cardiac drug (+)-cis-(2S,3S)-diltiazem from (E)-methyl 4-methoxyphenylpropenoate via either the (2R,3S)- or (2S,3R)-enantiomers of threo-methyl 3-(4-methoxyphenyl)-2,3- dihydroxypropanoate are described.

Process for the resolution of intermediates useful in the preparation of 1,5-benzothiazepines

A process for the resolution of amminoesters of the formula wherein R1 and R3 have the meanings reported in the specification, by tartaric acid and analogs thereof, is described. The compounds of formula IV-A are intermediates useful in the preparation of optically active 2-(4-methoxyphenyl)-1,5-benzothi-azepin-4(5H)ones.

Reaction of 3-Phenylglycidic Esters. III. Reaction of cis-3-Arylglycidic Esters with Various Thiophenols

The reaction of the cis-3-arylglycidic esters 2 and 10 with thiophenols (3) has been investigated.The reactivity and stereoselectivity of the oxirane ring-opening of these cis-glycidic esters were lower than those of the trans-analogues (1 and 9).These tendencies were more apparent in the 4-MeO derivative (2).On the other hand, the tin-catalyzed reaction of 2 with 3a was highly stereospecific and afforded the cis-opening products (5a).Keywords - cis-3-arylglycidic ester; thiophenol; oxirane ring-opening; tin catalyst; stereoselectivity

Reaction of 3-Phenylglycidic Esters. Part 2. Stereo- and Regio-selectivity in the Oxirane Ring Opening of Methyl trans-3-(4-Methoxyphenyl)glycidate with Various Thiophenols and the Effects of Solvent and Temperature

The effects of the solvent and temperature on the reaction of the trans-glycidate (1) with various substituted thiophenols (2) in the presence or absence of a catalyst have been investigated.The temperature had a surprisingly large effect on the stereochemistry of the oxirane ring-opening of (1).At room temperature, the erythro-isomer (4) (trans-opening product) was obtained as a major product in the absence of catalyst, while the cis-opening product (3) (threo-isomer) was produced predominantly at higher temperature.On the other hand, in a dipolar aprotic solvent, the regioisomer (5) was formed, the yield increasing with the electron-donating ability of the substituents on (2).The formation of compound (5) may involve single-electron transfer as a key step.