A kind of preparation method of PEG immobilized chiral bisoxazoline ligand
A bisoxazoline and ligand technology is applied in the field of preparation of PEG-immobilized chiral bisoxazoline ligands, and can solve the problem of low yield of synthesizing azabisoxazoline ligands, no recycling of catalysts, and single The problem of high cost of methyl ether, to achieve the effect of improving the solid loading rate and stability, high activity and stereoselectivity, and low production cost
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Embodiment 1
[0035] Synthesis
[0036] (1) Preparation of OMs-PEG-2000
[0037] Dissolve 20g of PEG-2000 in 400ml of toluene solution, raise the temperature to remove water, protect with nitrogen, and distill out 100ml / g of toluene. Cool down to room temperature, add 20ml of dichloromethane and 3.46ml of triethylamine, stir for 15min, then add 2.3ml of methanesulfonyl chloride, and stir at room temperature for 18h. After the reaction is over, add 5ml of methanol, stir for 30min, and use G 2 Floxacin funnel + diatomaceous earth filtration, after the filtrate was concentrated under reduced pressure, 300ml of isopropanol was added to dissolve and clear, precipitated in an ice-water bath, filtered through a Buchner funnel, rinsed with 50ml of ether, and dried in vacuo to obtain 18.6g of OMs-modified 2(OMs- The HPLC-ELSD spectrum of PEG-2000 is as follows Figure 4 ), the yield was 93%.
[0038]
[0039] (2) Preparation of I-PEG-2000
[0040] Add 10 g of 2 in step (1), 100 ml of aceto...
Embodiment 2
[0047] With embodiment 1, just change PEG-2000 into PEG-4000.
[0048] (1) Dissolve 20g of PEG-4000 in 400ml of toluene solution, raise the temperature to remove water, protect with nitrogen, and distill out 100ml of toluene. Cool down to room temperature, add 20ml of dichloromethane and 1.73ml of triethylamine, stir for 15min, then add 1.15ml of methanesulfonyl chloride and stir at room temperature for 18h. After the reaction is over, add 5ml of methanol, stir for 30min, and use G 2 Filtrate through a sand star funnel + diatomaceous earth, concentrate the filtrate under reduced pressure, add 300ml of isopropanol to dissolve it and clear it, and precipitate in an ice-water bath. Filtered with a Buchner funnel, rinsed with 50ml of ether, and dried in vacuo to obtain 19.0g of OMs-PEG-4000 with a yield of 95%.
[0049] (2) Add 15g of OMs-PEG-4000 in step (1) and 150ml of acetone to a 500ml single-necked bottle, stir to dissolve, add 2.23g of sodium iodide, and reflux for 18h. ...
Embodiment 3
[0052] Same as Example 1, except that PEG-2000 is changed to MeOPEG-10K.
[0053] (1) Dissolve 20g of MeOPEG-10K in 400ml of toluene solution, raise the temperature to remove water, protect with nitrogen, and distill 100ml of toluene. Cool down to room temperature, add 30ml of dichloromethane and 0.35ml of triethylamine, stir for 15min, then add 0.23ml of methanesulfonyl chloride and stir at room temperature for 18h. After the reaction is over, add 5ml of methanol, stir for 30min, and use G 2 Filtrate through the Floxacin funnel + diatomaceous earth, concentrate the filtrate under reduced pressure, add 350ml of isopropanol to dissolve it and clear it, and precipitate in an ice-water bath. Filtrate through a Buchner funnel, rinse with 50 ml of ether, and dry in vacuo to obtain 18.0 g with a yield of 90%.
[0054] (2) Add 18g of OMs-MeOPEG-10K in step (1) and 200ml of acetone to a 500ml single-necked bottle, stir to dissolve, add 0.54g of sodium iodide, and reflux for 18h. Co...
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