Synthetic method of atorvastatin calcium intermediate
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A technology of atorvastatin calcium and synthesis method, applied in microorganism-based methods, biochemical equipment and methods, microorganisms and other directions, can solve problems such as long steps, and achieve the effects of shortening steps, high yield and reducing costs
Inactive Publication Date: 2014-03-05
SUZHOU HEALTH COLLEGE
View PDF2 Cites 11 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
In the prior art ( S )-3,4-dihydroxybutyric acid methyl ester, 3,4-epoxybutyrate or ethyl chloroacetoacetate as raw material, the same intermediate [(4 R ,6 S )-6-hydroxymethyl-2,2-dimethyl-1,3-dioxan-4-yl] tert-butyl acetate, and then through oxidation, condensation and reduction reaction to obtain [(4 R ,6 R )-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert-butyl ester, a longer step, [(4 R ,6 S )-6-hydroxymethyl-2,2-dimethyl-1,3-dioxan-4-yl] tert-butyl acetate yields were 44.5%, 55.1% and 25.9%, respectively
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment Construction
[0016] The present invention will be described in detail below in conjunction with embodiments.
[0017] Step 1) Add THF (50 ml) into a 1 L three-necked flask, and add (3 S )-4-bromo-3-hydroxybutyric acid ethyl ester (purity 97%, 15.7 g, 75 mmol) and tert-butyl acetate (17.4 g, 150 mmol), continue to stir under argon protection at 0-5 ℃, dropwise Add 1 mol / L toluene-THF solution of tert-butylmagnesium chloride (1:2.5, 75 ml), and continue stirring at 5°C for 30 min. Add 1 mol / L lithium diisopropylamide in n-hexane (240 ml) dropwise, and continue stirring at the same temperature for 16 h after the drop. Separately take concentrated hydrochloric acid (60.4 g), water (31.3 g) and ethyl acetate (50 ml), stir and mix, add to the above reaction solution, stir for 10 min, then pour into a 2 L separatory funnel and let stand to separate. layer, the organic layer was washed with water (100 ml × 2) and concentrated under reduced pressure to obtain a reddish-brown oil (5 S )-tert-buty...
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
PUM
Login to view more
Abstract
The invention discloses a synthetic method of an atorvastatin calcium intermediate. The synthetic method comprises the following steps: preparing [(4R, 6S)-6- brooethyl-2,2-diemthyl-1,3-dioxane-4-group] tert-butyl acetate (5) by (3S)-4-bromine-3-hydroxyl ethyl butyrate through condensation, asymmetric biological catalytic reduction and hydroxyl protection; and preparing an atorvastatin calcium intermediate [(4R, 6S)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-group] tert-butyl acetate through catalytic hydrogenation reduction of raney nickel after 5 is condensed with nitromethane under action of cuprous bromide and a nitrogen-containing compound ligand. According to the synthetic method disclosed by the invention, steps are shortened, cost is lowered, and therefore, the synthetic method is more suitable for large-scale preparation.
Description
technical field [0001] The invention relates to the field of chemistry, in particular to a method for synthesizing an atorvastatin calcium intermediate. Background technique [0002] [(4 R ,6 R )-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl] tert-butyl acetate is a synthetic hypolipidemic drug atorvastatin calcium ( important intermediate of atorvastatin calcium). In the prior art ( S )-3,4-dihydroxybutyric acid methyl ester, 3,4-epoxybutyrate or ethyl chloroacetoacetate as raw material, the same intermediate [(4 R ,6 S )-6-hydroxymethyl-2,2-dimethyl-1,3-dioxan-4-yl] tert-butyl acetate, and then through oxidation, condensation and reduction reaction to obtain [(4 R ,6 R )-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert-butyl ester, a longer step, [(4 R ,6 S The yields of )-6-hydroxymethyl-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert-butyl ester were 44.5%, 55.1% and 25.9%, respectively. Existing technology with (3 S )-4-chloro-3-hydroxybutyric a...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to view more 
Login to view more