Preparation method of chiral α-substituted propionic acid compounds
A compound and chiral catalyst technology, which is applied in the field of asymmetric Ru catalytic hydrogenation preparation of chiral α-substituted propionic acid compounds, can solve the problems of high hydrogen pressure and limited substrate range, and achieve low cost and no environmental pollution , the effect of good application prospects
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[0031] In the preparation method of chiral α-substituted propionic acid of the present invention, the reaction temperature and reaction time are not particularly limited, as long as the reaction from the substrate to the product of the present invention can be carried out. However, from the viewpoint of reaction yield and reaction efficiency, the reaction temperature can be set to 0 to 50°C, preferably room temperature. In addition, the reaction time can be set to 1 to 96 hours, preferably the reaction time is 1 to 24 hours. The reaction pressure is set at 1-100 bar, preferably 1-50 bar, more preferably 1-20 bar.
[0032] In the preparation method of the chiral α-substituted propionic acid compound of the present invention, the α-substituted acrylic acid compound represented by the formula (I) undergoes an asymmetric catalytic hydrogenation reaction, thereby generating the chiral α-substituted propionic acid compound represented by the formula (II) acid compounds. The prepar...
Embodiment 1、2
[0038] Embodiment 1, 2a (R=C 6 h 5 ) preparation
[0039] In a 10mL hydrogenation bottle, add the catalyst (3.4mg, 2.0μmol) coordinated by the phosphine nitrogen ligand L12a and triphenylphosphine ruthenium chloride in advance, and add α-substituted acrylic acid 1a (29.6mg, 0.2mmol) With anhydrous sodium bicarbonate (8.4 mg, 0.1 mmol), the system was passed through a vacuum line and replaced with nitrogen three times. Use a syringe to inject freshly steamed and newly degassed methanol (3 mL) into the reaction tube containing the substrate and additives, and place the reaction system in an autoclave at 25 °C and H 2 (6 bar) and stirred for 24 hours, the solvent was removed under reduced pressure, and a small amount of mixed system NMR was taken to determine the conversion rate. Column chromatography of the remaining residue afforded pure product 2a. The conversion was 100% and the enantiomeric excess was 98% ee. 2a: 1 H NMR (400MHz, CDCl 3 )δ7.99–6.81 (m, 5H), 4.01–3....
Embodiment 2、2
[0040] Embodiment 2, 2b (R=4-CH 3 C 6 h 4 ) preparation
[0041] In a 10mL hydrogenation bottle, add the catalyst (3.4 mg, 2.0 μmol) coordinated by the phosphine nitrogen ligand L1a and triphenylphosphine ruthenium chloride in advance, and add α-substituted acrylic acid 1b (32.4 mg, 0.2 mmol) With anhydrous potassium bicarbonate (10.0 mg, 0.1 mmol), the system was passed through a vacuum line and replaced with nitrogen three times. Use a syringe to inject freshly steamed and newly degassed methanol (3 mL) into the reaction tube containing the substrate and additives, and place the reaction system in an autoclave at 0 °C and H 2 Stirring under the condition of (1 bar) for 24 hours, removing the solvent under reduced pressure, taking a small amount of mixed system NMR to determine the conversion rate. Column chromatography of the remaining residue afforded pure product 2b. The conversion was 100% and the enantiomeric excess was 98% ee.
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