- Method for synthesizing ADA
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The invention relates to a compound synthesized in the medicine field, and particularly relates to a rosuvastatin intermediate. The method for synthesizing ADA comprises the following five steps: 1, reacting S-4-chloro-3-hydroxy butyronitrile with hexamethyl-disilazane to generate an intermediate I; 2, reacting the prepared intermediate I, a reducing agent and methanesulfonic acid with tert-butyl bromoacetate to prepare an intermediate II; 3, preparing an intermediate III from the prepared intermediate II by enzyme selective reduction; 4, reacting the prepared intermediate III with acetone acetal to prepare an intermediate IV; and 5, reacting the prepared intermediate IV and tetrabutylammonium bromide with sodium acetate to prepare the target intermediate ADA. According to the method, operation for preparing ADA is more convenient; and the method has high safety coefficient and low cost, and is very suitable for industrial production.
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- Stereoselective reduction of δ-hydroxy β-ketoesters to syndiol in achiral micellar system
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A novel, efficient and stereo-selective process for synthesis of statin side chain, a key intermediate for statin type cholesterol lowering drugs such as Lipitor (atorvastatin) and Crestor (rosuvastatin) in achiral micellar media is reported. The key feature of this process is sodium borohydride reduction of δ-hydroxy β-ketoester in achiral micellar system in 92% de, thereby avoiding metal chelation methods which employ triakylborane, titanium (IV) isopropoxide or cerium (III) chloride prior to reduction.
- Roy, Bhairab Nath,Singh, Girij Pal,Lathi, Piyush Suresh,Agrawal, Manoj K,Mitra, Rangan
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p. 1247 - 1251
(2015/11/24)
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- A NOVEL, GREEN AND COST EFFECTIVE PROCESS FOR SYNTHESIS OF TERT-BUTYL (3R,5S)-6-OXO-3,5-DIHYDROXY-3,5-O-ISOPROPYLIDENE-HEXANOATE
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The present invention provides a process of preparation of an intermediate useful for the preparation of statins more particularly the present invention relates to an eco-friendly and cost effective process for the preparation of tert -butyl (3R,5S)-6-oxo-3,5-dihydroxy- 3,5-O-isopropylidene-hexanoate [I].
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Page/Page column 42
(2015/01/07)
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- PROCESS FOR THE PREPARATION OF DIOXANE ACETIC ACID ESTERS
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Process for the preparation of an ester of formula (1), wherein R1represents a leaving group, CN, OH or a COOR5 group, R3 and R4each independently represent a 1-3 C alkyl group, and R2 and R5 each independently represent an ester residue, wherein the corresponding salt with formula (2), wherein M represents H or an alkali (earth) metal in an inert solvent is contacted with an acid chloride forming agent to form the corresponding acid chloride, and the acid chloride is contacted with an alcohol with formula R2OH in the presence of N-methyl-morpholine. Preferably M represents an alkali metal, and R2 represents an alkyl group, particularly a t.-butyl group. (1), (2)
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- Diastereomer-differentiating hydrolysis of 1,3-diol-acetonides: A simplified procedure for the separation of syn-and anti-1,3-diols
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(formula presented) A new method to facilitate the separation of diastereomeric syn- and anti-1,3-diols is described. The method relies on the different hydrolysis rates of the corresponding diastereomeric acetonides. Treatment of a dichloromethane solution of syn- and anti-1,3-diol-acetonide with a catalytic amount of diluted aqueous hydrochloric acid leads to the selective cleavage of the anti diastereomer. The resulting anti-1,3-diol can be easily separated from the unchanged syn-1,3-diol-acetonide.
- Bode, Silke E.,Muller, Michael,Wolberg, Michael
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p. 619 - 621
(2007/10/03)
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- Process for producing 6-cyanomethyl-1,3-dioxane-4-acetic acid derivatives
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The present invention provides a process which can produce an important intermediate for the production of the HMG coenzyme A reductase inhibitor atrovastatin, 6-cyanomethyl-1,3-dioxane-4-acetic acid derivatives, with ease industrially and in good yields, wherein a 3,5-dihydroxy-6-halohexanoic acid derivative is used as the starting material, and which comprises cyanation by reaction with a cyanating agent for substitution of a cyano group for the halogen atom and an acetal formation reaction of the diol moiety with an acetal forming reagent in the presence of an acid catalyst.
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Page column 13
(2008/06/13)
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- Biocatalytic reduction of β,δ-diketo esters: A highly stereoselective approach to all four stereoisomers of a chlorinated β,δ-dihydroxy hexanoate
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A stereoselective chemoenzymatic synthesis of all four stereoisomers of tert-bulyl 6-chloro-3,5-dihydroxyhexanoate (6a) is presented. The key step of the sequence is a highly regio-and enantioselective single-site reduction of tert-butyl 6-chloro-3,5-dioxohexanoate (1a) by two enantiocomplementary biocatalysts. Alcohol dehydrogenase from Lactobacillus brevis (recLBADH) afforded a 72% yield of enantiopure tert-butyl (5)-6-chloro-5-hydroxy-3-oxohexanoate [(S)-2a]. The enantiomer (R)-2a was prepared with 90-94% ee by Baker's yeast reduction in a biphasic system (50% yield). Both biotransformations were performed on a gram scale. The β-keto group of the enantiomeric δ-hydroxy-β-keto esters 2a thus obtained was reduced by synand anti-selective borohydride reductions. Permutation of the reduction methods yielded all four stereoisomers of the crystalline target compound 6a (≥99.3% ee, dr≥205:1), which is a versatile 1,3-diol building block. recLBADH accepts a variety of β,δ-diketo esters as was determined in a photometric assay. tert-Butyl 3,5-dioxohexanoate (1b) and tert-butyl 3,5-dioxoheptanoate (1c) were reduced on a preparative scale as well to afford the corresponding δ-hydroxy-β-keto esters (R)-2b and (R)-2c with 99.4% ee and 98.1% ee, respectively. Wiley-VCH Verlag GmbH, 2001.
- Wolberg, Michael,Hummel, Werner,Mueller, Michael
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p. 4562 - 4571
(2007/10/03)
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- Process for the preparation of 1,3-dioxane derivatives useful in the preparation of HMG-COA reductase inhibitors
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A novel, overall process for the preparation of a compound of the formula I: STR1 where R1 and R2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group; and R3 is hydrogen, an alkyl group, or an aryl group, or salts thereof, useful as intermediates in the preparation of HMG-CoA reductase inhibitors; novel methods within the overall process; and novel intermediates produced by those methods.
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