42399-48-4

Basic information

• Product Name: [S-(R*,R*)]-3-[(o-aminophenyl)thio]-3-(p-methoxyphenyl)lactic acid
• Synonyms: [S-(R*,R*)]-3-[(o-aminophenyl)thio]-3-(p-methoxyphenyl)lactic acid;(D)-(+)-á-[(2-Aminophenyl)-thio]-à-hydroxy-4-methoxyphenylpropionic acid;(αS,βS)-β-[(2-Aminophenyl)thio]-α-hydroxy-4-methoxybenzenepropanoic acid
• CAS NO: 42399-48-4
• Molecular Formula: C₁₆H₁₇NO₄S
• Molecular Weight: 319.37548
• EINECS: 255-798-5
• Product Categories: PHARMACEUTICAL INTERMEDIATES
• Mol File: 42399-48-4.mol

Chemical Properties

• Boiling Point: 529.3°Cat760mmHg
• Flash Point: 273.9°C
• Appearance: /
• Density: 1.37g/cm³
• Vapor Pressure: 4.92E-12mmHg at 25°C
• Refractive Index: 1.668
• CAS DataBase Reference: [S-(R*,R*)]-3-[(o-aminophenyl)thio]-3-(p-methoxyphenyl)lactic acid(CAS DataBase Reference)
• NIST Chemistry Reference: [S-(R*,R*)]-3-[(o-aminophenyl)thio]-3-(p-methoxyphenyl)lactic acid(42399-48-4)
• EPA Substance Registry System: [S-(R*,R*)]-3-[(o-aminophenyl)thio]-3-(p-methoxyphenyl)lactic acid(42399-48-4)

Safety Data

• Hazardous Substances Data: 42399-48-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
[S-(R,R)]-3-[(o-aminophenyl)thio]-3-(p-methoxyphenyl)lactic acid is used as an intermediate in the synthesis of Diltiazem (D460620), a calcium channel blocker with vasodilating activity. It is employed for its antianginal, antihypertensive, and antiarrhythmic (class IV) properties, making it a valuable compound in the development of cardiovascular medications.

InChI:InChI=1/C16H17NO4S/c1-21-11-8-6-10(7-9-11)15(14(18)16(19)20)22-13-5-3-2-4-12(13)17/h2-9,14-15,18H,17H2,1H3,(H,19,20)

Upstream product

• 123742-82-5 (2S,3R)-2-Acetoxy-3-chloro-3-(4-methoxy-phenyl)-propionic acid methyl ester 
• 69738-04-1 potassium o-aminobenzenethiolate 
• 99109-07-6 (+)-(2S,3S)-2-hydroxy-3-(4-methoxyphenyl)-3-(2-aminophenylthio)propanoic acid methyl ester 
• 138382-02-2 (αS,βS,1R,2S)-β-<(2-aminophenyl)thio>-α-hydroxy-β-(4-methoxyphenyl)propanoic acid 2-phenylcyclohexyl ester hydrochloride 
• 4875-10-9 o-nitrothiophenol 
• 125411-72-5 (2S,3S)-2-hydroxy-3-(4-methoxyphenyl)-3-(2-acetylaminophenylthio)propionic acid 
• 1251618-05-9 (2S,3S)-3-(4-methoxyphenyl)oxirane-2-carboxylic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester 
• 30193-56-7 (2RS,3RS)-3-(2'-aminophenylthio)-2-hydroxy-3-(4''-methoxyphenyl)-propionic acid methyl ester 
• 137-07-5 2-amino-benzenethiol 
• 96125-49-4 methyl trans-3-(4-methoxyphenyl)glycidate 
• 122517-81-1 (2R,3S)-methyl 2,3-dihydroxy-3-(4-methoxyphenyl)propanoate 
• 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 
• 125354-93-0 (2S,3S) methyl 2-hydroxy-3-(4-methoxyphenyl)-3-(2-nitrophenylthio)propionate 

Downstream Products

• 7732-18-5 water 
• 42399-49-5 (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one 
• 27068-88-8 2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one 
• 27068-88-8 (+/-)-trans-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one 
• 27068-88-8 3c-hydroxy-2r-(4-methoxy-phenyl)-2,3-dihydro-5H-benzo[b][1,4]thiazepin-4-one 
• 33286-22-5 diltiazem hydrochloride 
• 42399-40-6 O-desacetyldiltiazem 

Relevant articles and documents

Selective synthesis method of diltiazem chiral intermediate

The invention provides a selective synthesis method of diltiazem chiral intermediate. The method is as below: using anisic aldehyde, chloroacetyl chloride and L-menthol as raw materials; first subjecting chloroacetyl chloride and L-menthol to an esterification reaction to obtain an intermediate 1; then subjecting the intermediate 1 with anisic aldehyde to a Darzens condensation reaction to produce diastereomer intermediates 2 and 3; refining to obtain an optically pure intermediate 3; reacting the intermediate 3 with o-aminothiophenol to obtain an intermediate 4; hydrolyzing the intermediate 4 to obtain an intermediate 5; and cyclizing the intermediate 5 to obtain a product. The invention has the advantages that the ester formed by chloroacetyl chloride and L-menthol is selective in the Darzens condensation reaction with anisic aldehyde to generate the more target product, and solubility difference between the target product and the isomer is used to directly obtain optically pure intermediate, without a complicated resolution process, and the yield is greatly improved. The method substantially increases the utilization rate of the main raw material anisic aldehyde and reduces cost.

Enantioselective Catalytic Epoxidation of Cinnamate Esters

A broad study of the (salen)Mn(III)-catalyzed asymmetric epoxidation of cis-cinnamate esters reveals that the steric properties of the ester group have a profound influence on enantioselectivity in the epoxidation reaction, with bulkier esters affording highest ee's.The sensitivity of the reaction selectivity to the steric properties of the cis-alkene are consistent with a "skewed" side-on approach of olefin to the metal -oxo.The electronic properties of the substrate arene ring substituents do not correlate with epoxidation ee, but instead with the cis/trans partitioning of product formation.Evidence is provided for a non-polar inter mediate in a stepwise oxygen-atom-transfer mechanism.The presence of pyridine N-oxide derivatives has a significant effect on catalysts rates and total turnovers, but negligible influence on the stereoselectivity of epoxidation.A mechanistic basis for the role of these additives is proposed.The synthetic applicability of the cinnamate epoxidation methodology is illustrated in the highly enantioslective synthesis of diltiazem.

Process for the preparation of benzothiazepin-one derivatives

The object of the invention is a process for the preparation of the trans(-) (2R,3S) diastereoisomer of the glycidic esters of general formula: STR1 wherein a chlorohydrin of general formula: STR2 is reacted with a strong organic base in a suitable solvent and at a temperature between -10° C. and room temperature. Another object of the invention is intermediate compounds cis(+) (2S,3S) 1,5-benzothiazepin-4-one.

Process for the preparation of intermediates for the synthesis of diltiazem

A process for the preparation of (2S,3S)-threo-2-hydroxy-3-(2--aminophenylthio)-3-(4-methoxyphenyl)-propionic acid by resolution of the racemic mixture is described. The resolution is carried out by using as resolving agent (1S,2S)--threo-1-phenyl-2-amino-1,3-propanediol or (1S,2S)-threo-1-(4--methylthiophenyl)-2-amino-1,3-propanediol.

2-hydroxy-3-(4-methoxyphenyl)-3-(2-aminophenylthio)propionic acid, 8'-phenylmenthyl ester, especially for diltiazem

The titled ester, especially having the (2S,3S)-configuration, which is an intermediate for the production of diltiazem, is provided. Very high yields are obtainable.

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 preparation of intermediates for the synthesis of diltiazem

A process for the preparation of (2S,3S)-threo-2-hydroxy-3-(2-aminophenylthio)-3-(4-methoxyphenyl)-propionic acid by resolution of the racemic mixture is described. The resolution is carried out by using as resolving agent (1S,2S)-threo-1-phenyl-2-amino-1,3-propanediol or (1S,2S)-threo-1-(4-methylthiophenyl)-2-amino-1,3-propanediol.