Method for kinetic resolution of enantiomers of alpha-hydroxy-beta-dicarbonyl compounds under micro-reaction conditions or conventional reaction conditions
A technique for kinetic separation of dicarbonyl compounds, which is applied in the field of kinetic separation of enantiomers of α-hydroxy-β-dicarbonyl compounds, and can solve the problem of kinetic separation of α-hydroxy-β-dicarbonyl compounds. See reports and other issues to achieve the effects of high splitting efficiency, improving enantioselectivity, improving utilization rate and product yield
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Embodiment 1
[0039] Embodiment 1: Conventional reaction device carries out kinetic resolution reaction of 5-chloro-2-methoxycarbonyl-2-hydroxyl-1-indanone
[0040]
[0041] Add 5-chloro-2-methoxycarbonyl-2-hydroxy-1-indanone enantiomer (2.4g, 9.99mmol) and 200mL toluene in a 250mL three-necked flask, add H 8 -Ph(R 6 =R 7 =Phenyl)phosphorimidic acid catalyst (0.50g, 0.5mmol), phenylhydrazine (1.08g, 9.99mmol) was added under stirring, and the reaction was stirred at 20°C for 24h. After concentrating until the solvent is completely dry and column chromatography (the process parameter is that the volume ratio of petroleum ether and ethyl acetate is 1:1), the chiral hydrazone compound C is obtained. 1 1.78g, yield 54.0%, ee value 87%; a single configuration of α-hydroxy-β-dicarbonyl compound D was obtained 1 1.10 g, yield 46.0%, ee value 95%.
[0042] C 1 hydrogen spectrum 1 H NMR (400MHz, CDCl 3 ): δ7.73(m,2H),7.30(m,2H),7.14(m,2H),7.04(m,1H),6.92(m,2H),3.79(s,3H),3.54(dd, J=17.2...
Embodiment 2
[0044] Example 2: Kinetic resolution of 5-chloro-2-methoxycarbonyl-2-hydroxyl-1-indanone using micro-reaction device
[0045]
[0046] The 5-chloro-2-methoxycarbonyl-2-hydroxyl-1-indanone enantiomer (2.4g, 9.99mmol) and H 8 -Ph(R 6 =R 7 =Phenyl)phosphorimidic acid catalyst (0.50g, 0.5mmol) was dissolved in toluene to obtain a homogeneous solution (200mL; phenylhydrazine (1.08g, 9.99mmol) was dissolved in toluene to obtain a homogeneous solution (100mL ); the two homogeneous solutions were injected into a tubular microreactor with a length of 150 cm and an inner diameter of 2 mm with a metering pump at a flow rate of 2:1, the reaction temperature was 20° C., and the reaction time was 30 min, and the effluent liquid was collected. After being concentrated until the solvent was completely dry, After column chromatography (process parameter is that the volume ratio of sherwood oil and ethyl acetate is 1:1), obtain chiral hydrazone compound C 1 1.66g, yield 50.4%, ee value 9...
Embodiment 3
[0049] Example 3: Kinetic resolution reaction of 5-methyl-2-methoxycarbonyl-2-hydroxyl-1-indanone using micro-reaction device
[0050]
[0051] 5-Ethyl-2-methoxycarbonyl-2-hydroxyl-1-indanone enantiomer (2.2g, 9.99mmol) and H 8 -3,5-(CF 3 ) 2 C 6 h 3 )[R 6 =R 7 =3,5-bis(trifluoromethyl)phenyl]phosphorimidic acid catalyst (0.77g, 0.5mmol) was dissolved in chloroform to obtain a homogeneous solution (240mL); p-chlorophenylhydrazine (0.89 g, 4.99mmol) was dissolved in chloroform to obtain a homogeneous solution (60mL); the two homogeneous solutions were injected into a tubular microreactor with a length of 200cm and an internal diameter of 3mm with a metering pump at a flow rate of 4:1. 10°C, the reaction time is 40min, and the effluent liquid is collected. After concentrating until the solvent is completely dry and column chromatography (the process parameter is that the volume ratio of petroleum ether and ethyl acetate is 1:1), the chiral hydrazone compound C is obtai...
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