摘要
亚磷酸三乙酯与氯乙酸乙酯进行缩合、重排、脱氯乙烷合成磷酸酯,再与对氟苯甲醛经Knoevenagel反应合成肉桂酸酯,肉桂酸酯与丙二酸二乙酯胺解合成的N-甲胺基羰基乙酸乙酯环合得到哌啶二酮,环化物用硼氢化钾复合还原剂还原得±4-(4-氟苯基)-3-羟甲基-1-甲基哌啶,把混旋体进行手性拆分得目标产物(-)反式-4R(4-氟苯基)-3-羟甲基-1-甲基哌啶。选择自制硅胶酸载催化剂Cat1#、醋酸-乙二胺催化剂Cat2#、复合相转移催化剂Cat3#为各步催化剂,反应收率分别为89.1%、96.3%、86.5%、76.3%、87.2%、43.7%,总收率24.3%,比旋光度-36￣-38°,纯度大于99%。
The preparation of （-）trans-4R （4＇-fluorophenyl）-3S-hydroxymethyl-l-methylpiperidine from triethyl phosphite, diethyl malonate, 4-fluorobenzaldehyde and ethyl chloroacetate was pvesented under the condition of existing Cat1#, 2#, 3# catalysts. The effect of catalyst 1#, 2#, 3# and reduction agent, chiral resolving agent and PH control on the reaction was discussed. Overall yield was 24.27%, optical rotation -36-38°, HPLC purity more than 99%.
出处
《精细化工中间体》
CAS
2007年第3期41-44,共4页
Fine Chemical Intermediates
