123049-81-0

Basic information

• Product Name: simvastatin
• CAS NO: 123049-81-0
• Molecular Weight: 418.574
• Mol File: 123049-81-0.mol

Chemical Properties

• CAS DataBase Reference: simvastatin(CAS DataBase Reference)
• NIST Chemistry Reference: simvastatin(123049-81-0)
• EPA Substance Registry System: simvastatin(123049-81-0)

Safety Data

• Hazardous Substances Data: 123049-81-0(Hazardous Substances Data)

Upstream product

• 139893-43-9 simvastatin ammonium salt 
• 79902-59-3 6(R)-<2-<8(S)-((2,2-Dimethylbutyryl)oxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphth-1(S)-yl>ethyl>-4(R)-((tert-butyldimethylsilyl)oxy)-3,4,5,6-tetrahydro-2H-pyran-2-one 
• 479482-40-1 (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-6,6-(ethylenedioxy)-3,4,5,6,-tetrahydro-4-hydroxy-2H-pyran-2-yl]ethyl}-1,2,3,7,8,8a-hexahydro-3,7-dimethylnaphthalen-1-yl 2,2-dimethylbutanoate 
• 75330-75-5 lovastatin 
• 479482-41-2 (2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl 2,2-dimethylpropanoate 
• 81189-93-7 (2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl benzoate 
• 479482-42-3 (2R,4R)-2,2-(ethylenedioxy)-6-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-2H-pyran-4-yl 2,2-dimethylpropanoate 
• 479482-39-8 (2R,4R)-2,2-(ethylenedioxy)-6-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-2H-pyran-4-yl benzoate 
• 595-37-9 2,2-dimethylbutyric acid 
• 5856-77-9 2,2-dimethylbutanoyl chloride 
• 134970-33-5 N-butyl-7-<1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-<<2,2-dimethylbutanoyl>oxy>-1(S)-naphthyl>-3(R),5(R)-dihydroxyheptanoic acid amide 
• 134970-31-3 N-butyl-7-<1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-<<2,2-dimethylbutanoyl>oxy>-1(S)-naphthyl>-3(R),5(R)-bis<(tert-butyldimethylsilyl)oxy>heptanoic acid amide 
• 145576-24-5 C₂₁H₃₀O₅ 
• 850920-00-2 C₂₃H₃₂O₆ 

Downstream Products

• 149949-01-9 6(S)-hydroperoxysimvastatin 
• 149949-05-3 2,2-Dimethyl-butyric acid (1S,3R,4S,7S,8S)-4-hydroxy-8-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-3,7-dimethyl-1,2,3,4,7,8-hexahydro-naphthalen-1-yl ester 
• 67-64-1 acetone 
• 75-65-0 tert-butyl alcohol 
• 121009-77-6 simvastatin acid 
• 101314-97-0 simvastatin sodium salt 
• 139893-43-9 simvastatin ammonium salt 
• 134523-09-4 6β'-hydroxy simvastatin 
• 121624-18-8 6'-Exomethylene-Simvastatin 
• 1426939-44-7 C₂₅H₃₆O₅ 
• 476305-24-5 C₅₀H₇₆O₁₀ 

Relevant articles and documents

Synthesis of Synvinolin: Extremely High Conversion Alkylation of an Ester Enolate

An efficient process for the commercial preparation of the therapeutically important cholesterol lowering drug synvinolin (2: simvastatin, ZOCOR) from mevinolin (1: lovastatin, MEVACOR) is reported.The synthesis relies upon deactivation of the δ-lactone carbonyl toward enolization via conversion to the bisbutylamide 7.An extremely high conversion (99.7percent) ester enolate alkylation of 7 affords 8 and 9.Subsequent desilylation and intramolecularly assisted basic amide hydrolysis in the presence of the dimethylbutyrate ester moiety yields 12, which is lactonized to 2.The overall yield from 1 to 2 is 86percent.

New synthesis of simvastatin

A noninfringing synthesis of simvastatin 1, starting from lovastatin 2, is presented. This synthesis features the protection of the free hydroxyl group of the lovastatin with 3,4-dihydro-2H-pyran (DHP) and opening of the lactone ring with n-BuNH2 to afford amide 4 as a key intermediate. Copyright Taylor & Francis Group, LLC.

A cost-efficient synthesis of simvastatin via high-conversion methylation of an alkoxide ester enolate

A cost-efficient synthesis of simvastatin (2), starting from mevinolin (lovastatin) (la) or its precursor mevinolinic acid (Ib), is reported. This synthesis involves the use of a new intermediate, lovastatin cyclopropylamide (3), eliminating two chemical steps of protection and deprotection of the open dihydroxy form of (la). Synthesis is based on the high-conversion methylation of an alkoxide ester enolate and involves only four chemical steps. Methylation reaction conditions have been optimized to get +~ 99.5% conversion. Process is economical on large-scale and product (2) is obtained in 85% overall yield.

A convenient procedure for the methylation of lovastatin: Synthesis of simvastatin

A new synthetic method for the preparation of the cholesterol lowering drug simvastatin 1 from the naturally occurring lovastatin 2 is reported. The synthesis relies upon deactivation of the α-carbon of the δ-lactone via conversion of the lactone group of lovastatin 2 to its carboxylic acid-amine salt derivative and then methylation of the 2-methylbutyrate-side chain of 3.

For the preparation of simvastatin method

The present invention discloses a simvastatin preparation method, which comprises using lovastatin and alkyl amine to prepare lovastatin amide, protecting the hydroxyl in the lovastatin amide molecules, carrying out methylation on the protected lovastatin amide to obtain protected simvastatin amide, carrying out deprotection, alkaline hydrolysis and ammonium salt forming on the protected simvastatin amide to obtain a simvastatin ammonium salt, and carrying out cyclization on the simvastatin ammonium salt to generate simvastatin. According to the present invention, the methyl cyclohexane is adopted as the methylation reaction solvent, such that the tetrahydrofuran consumption is reduced, the cost is reduced, the production safety is improved, and the solvent recovery and reuse process is simplified.

Functional Micelles for Hard Tissue Targeted Delivery of Chemicals

Compositions and methods for targeting agents to hard tissue are provided.

Preparation method for simvastatin

The invention discloses a preparation method for simvastatin. The preparation method for simvastatin comprises the following steps: subjecting a simvastatin ammonium salt to cyclization, decoloring and concentration so as to obtain a crude simvastatin product; and then subjecting the crude simvastatin product to refining so as to obtain medical simvastatin. Compared with conventional preparation methods, the preparation method provided by the invention has the advantages of substantial improvement of product yield, effective reduction in impurities in the medical simvastatin and enhancement of product quality; and the preparation method can simplify technological operation and is suitable for industrialization.

METHODS FOR PREPARING STATIN COMPOUNDS BY LACTONIZATION

A method for preparing a statin compound by lactonization is disclosed, which comprises the following step: lactonizing a compound of formula II into the compound of formula I in the presence of a strong acid catalyst and a dehydrant in a first solvent, wherein Z represents H, ammonium, or a metal cation, R1 is H or C1-C6 alkyl, preferably H or CH3, R2 is CH3, OH, CH2OH, CH2OC(O)R3, CH2OR3, or COOR4, preferably CH3 or OH, R3 and R4 are independently selected from the group consisting of H and C1-C6 alkyl.

METHODS FOR PREPARING STATIN COMPOUNDS BY LACTONIZATION

A method for preparing a statin compound by lactonization is disclosed, which comprises the following step: lactonizing a compound of formula II into the compound of formula I in the presence of a strong acid catalyst and a dehydrant in a first solvent, wherein Z represents H, ammonium, or a metal cations; R1 is H or C1-C6 alkyl, preferably H or CH3, R2 is CH3, OH, CH2OH, CH2OC(O)R3, CH2OR3, or COOR4, preferably CH3 or OH, R3 and R4 are independently selected from the group consisting of H and C1-C6 alkyl.

Process for Preparing Substantially Pure Simvastatin

This invention relates to an improved process for preparing substantially pure simvastatin (I), chemically known as (1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2-H-pyran-2-yl]ethyl]-3 ,7-dimeth-yl-1,2,3,7,8,8a-Hexahydronaphthalen-1-yl2,2-dimethyl butanoate, which comprises of: a) treating lovastatin (II) with an alkali metal hydroxide in a chosen suitable alcoholic solvent followed by relactonization to obtain the diol lactone intermediate (III) in a single vessel. b) selective silylation of 4-hydroxy group of diol lactone intermediate (III) with a chosen suitable silylating reagent to obtain mono silylated intermediate diol lactone (IV). c) acylation of the mono silylated intermediate (IV) to form silylated simvastatin (V) Or optionally, preparing silylated simvastatin (V) starting from Lovastatin (II) without isolating diol lactone (III) and monosilylated diol lactone (IV) and d) finally, removal of the silyl protecting group on silylated simvastatin (V) followed by purification to provide substantially pure simvastatin (I).