In order to further study Celestolide alcoholization and resolution after alcoholization, the present invention uses Celestolide ketone as a raw material, further reacts its latent chiral ketone group to obtain chiral hydroxyl neutrality, and then further resolves to obtain a hydroxy chiral center. single configuration compound.
The specific implementation process is as follows:
1) Under low temperature conditions, with alcohol as a solvent, add raw material salymuskone and sodium borohydride in a certain proportion, then keep low temperature conditions for reaction, and get 1-(6_tert-butyl-1,1-dimethyl- 2,3-dihydro-1H-inden-4-yl)ethanol;
2) In the organic solvent toluene, use the 1-(6-tert-butyl-1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)ethanol obtained in step 1) as raw material, press Add acyl donor, lipase, and racemization catalyst in a certain proportion, and perform a kinetic resolution reaction at a certain temperature to obtain (1R)-1-(6-tert-butyl-1,1-dimethyl-2, 3-dihydro-1H-inden-4-yl) acyl compounds of ethanol;
3) The acyl compound of (1R)-1-(6-tert-butyl-1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)ethanol obtained in step 2) was added to the press In a mixed solution of tetrahydrofuran and lithium hydroxide prepared in a certain proportion, the reaction is carried out at room temperature, and the progress of the reaction is detected. After the reaction is completed, the pure product (1R)-1-(6-tert-butyl-1, 1-dimethyl-2,3_dihydro_1H_4_yl) ethanol, the optical purity of the final product can reach more than 99%; the acyl group donor described in step 2) is p-chlorophenol B Acid acid ester, its addition is 1.0～1.5 times of raw material 1-(6_tert-butyl-1,1-dimethyl-2,3-dihydro-1H-inden-4-yl) ethanol molar weight The lipase described in step 2) is Pseudomonas fluorescens lipase Lipase AK, and its addition is raw material 1-(6-tert-butyl-1,1-dimethyl-2,3-dihydro- 1%～10% of 1H-inden-4-yl) ethanol mass; The racemization catalyst described in step 2) is solid superacid S042-_Fe2O3, its addition is raw material 1-(6-tert-butyl-1 , 1-dimethyl-2, 3-dihydro-1H-inden-4-yl) 5%~20% of the mass of ethanol.
The present invention uses Celestolide ketone as a raw material to obtain (1R)-1-(6-tert-butyl-1,1-dimethyl-2,3-dihydro-1H-indene-4 through hydrogenation reduction and dynamic kinetic resolution. -yl) glycolyl compound, and then hydrolyzed to finally obtain (1R)-1-(6-tert-butyl-1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)ethanol. The method has the characteristics of simple operation, high product yield, good optical purity, etc., and has great guidance and application value in the preparation research of Celestolide ketone derivatives.