78437-40-8

Upstream product

• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 22027-50-5 methyl 3-(4-methoxybenzoyl)acetate 

Downstream Products

• 336113-23-6 (S)-2-Chloro-3-hydroxy-3-(4-methoxy-phenyl)-propionic acid methyl ester 
• 152397-94-9 (3S)-methyl 2,2-dichloro-3-hydroxy-3-(4-methoxyphenyl)propionate 
• 152397-85-8 methyl 2,2-dichloro-3-(4-methoxyphenyl)-3-oxopropionate 
• 13305-16-3 (S)-(-)-methyl 3-(4-methoxyphenyl)-3-hydroxypropanoate 
• 135505-14-5 (3R) methyl β-hydroxy-β-(p-methoxyphenyl) propionate 
• 96125-49-4 methyl trans-3-(4-methoxyphenyl)glycidate 
• 13305-16-3 methyl 3-(4-methoxyphenyl)-3-hydroxypropanoate 
• 137173-39-8 methyl (2R,3R)-2-chloro-3-hydroxy-3-(4-methoxyphenyl)propionate 
• 134931-62-7 methyl (2S,3S)-2-chloro-3-hydroxy-3-(4-methoxyphenyl)propionate 
• 22027-50-5 methyl 3-(4-methoxybenzoyl)acetate 

Relevant academic research and scientific papers

Stereoselective Synthesis of Diltiazem via Dynamic Kinetic Resolution

An efficient synthesis of diltiazem has been developed using dynamic kinetic resolution (DKR) as a key step. The methyl (2S,3S)-2-chloro-3-hydroxy-3- (4-methoxyphenyl)propionate was synthesized from a racemic mixture of α-chloro-β-keto ester, with high anti diastereoselectivity (92%) and enantioselectivity (95%), based on an asymmetric hydrogenation reaction with a chiral ruthenium(II) catalyst, simply prepared by mixing Ru(cod)(2-methylallyl) 2 with the atropisomeric ligand (S)-MeO-BIPHEP. By treatment of this α-chloro-β-hydroxy ester with a base, the corresponding trans methyl glycidate, a key intermediate of diltiazem, was easily obtained.

Asymmetric reduction of 2-chloro-3-oxo-ester into enantiomerically high pure diltiazem precursor by a Candida ketoreductase

Methyl (2R,3S)-3-(4-methoxyphenyl)glycidate [(2R,3S)-MPGM] is an advanced chiral synthon for the synthesis of the cardiovascular drug diltiazem. It can be easily accessed by cyclizing the reduction products of methyl 2-chloro-3-(4-methoxyphenyl)-3-oxo-propanoate (1a). Herein, we report an identified carbonyl reductase (CpKR) from Candida parapsilosis that displayed an excellent stereoselectivity toward the keto substituent at the C3-position of the 2-chloro-3-oxo-ester 1a. The engineered Escherichia coli cells harboring CpKR gene were directly applied for the asymmetric reduction of keto ester 1a with a space-time yield of 46 g L?1 d?1, which represents the highest productivity in bio-reduction of 1a reported so far. The isolated chiral alcohol products were then applied to the chemical synthesis of (2R,3S)-MPGM in 99% ee and a total yield of 76% in the two-step chemo-enzymatic reactions, which far exceeded the maximum theoretical yield (50%) of the existing industrial process based on a lipase-catalyzed resolution of racemic MPGM. This work provides a promising eco-friendly and cost-effective route toward industrial synthesis of pharmaceutically relevant diltiazem.

Trimethylchlorosilane-Mediated Mild α-Chlorination of 1,3-Dicarbonyl Compounds Promoted by Phenyliodonium Diacetate

Trimethylchlorosilane was used as chlorine source for the α-chlorination of 1,3-dicarbonyl compounds with phenyliodonium diacetate as oxidant at room temperature. The reaction allows the selective synthesis of α-monochlorinated products from different kinds of 1,3-dicarbonyl compounds in good yield. The potential possibility of this conversion for bromination has also been investigated.

Asymmetric reduction of aromatic ketones. II. An enantioselective synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate

Asymmetric reduction of some 3-keto esters (6, 8, and 11) to 3-hydroxy esters (7, 9, and 12) with various chiral reducing agents was investigated. The products (9 and 12) were converted to methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (2R,3S-3), a key intermediate in the practical enantioselective synthesis of diltiazem (1).

Process for preparing 2-halogeno-3-hydroxy-3-phenyl-propionic acid ester compounds

Disclosed is a process for preparing 2-halogeno-3-hydroxy-3-phenylpropionic acid ester compounds represented by the formula (I): STR1 wherein Ring A is a phenyl group which may be substituted, R1 is an ester residue, and X is a halogen atom, which comprises permitting an enzyme having the ability of stereoselectively reducing oxo group to hydroxy group to act on 2-halogeno-3-oxo-3-phenylpropionic acid ester compounds represented by the formula (II): STR2 wherein Ring A, R1 and X have the same meanings as defined above.

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.