H-Cube® Mini Plus Application Note
Image: H-Cube® Mini Plus from the H-Cube ® series
The following application note will give details on how the H-Cube® was used in the reduction of dihydropyrimidones to the corresponding tetrahydropyrimidones in high diastereoselectivity. Reactions were performed at Boston University.
Originally, the above reaction was tried using standard batch hydrogenation equipment, but resulted in multiple hydrogenation products with little or no chemoselectivity or stereoselectivity. The reaction was then performed on the H-Cube® to see if results could be improved. In order to find the optimal reaction conditions a series of catalysts were tested: Pd/C1 Pt/Al2O3, Pt/C and Raney Ni were tested over a series of temperatures and pressures. The initial results indicated that Raney-Ni provided the best conversions with fewer side reactions. Further optimization of reaction pressure, temperature and solvent gave 90 bar and 45°C as the optimal reaction conditions.
RESULTS AND DISCUSSION
As seen in Scheme 1., the hydrogenation of dihydropyrimidone resulted in the syn addition of the dihydrogen from the opposite face of the R2 substituent. From LC-MS with ELSD (Evaporative Light Scattering Detector) results the diasteroselectivity was found to be greater than 20:1. The epimerization of the compounds resulted in the thermodynamically more stable isomer via treatment in MeOH with catalytic amount of K2CO3. Yields after the two steps were between 76 and 91% for all compounds.
REFERENCE
Lou, S., Dai, P., Schaus, S.E., J. Org. Chem, 2007, 72, 9998-10008
Scheme 1. Hydrogenation of Dihydropyrimidones with H-Cube®
CONCLUSION
As seen in Scheme 1., the hydrogenation of dihydropyrimidone resulted in the syn addition of the dihydrogen from the opposite face of the R2 substituent. From LC-MS with ELSD (Evaporative Light Scattering Detector) results the diasteroselectivity was found to be greater than 20:1. The epimerization of the compounds resulted in the thermodynamically more stable isomer via treatment in MeOH with catalytic amount of K2CO3. Yields after the two steps were between 76 and 91% for all compounds. These experiments demonstrate the ability of H-Cube® to improve upon standard batch reactors significantly in terms of stereoselective control and yield.
