摘要
目的研究利培酮的合成工艺。方法以4-哌啶甲酸为原料,经氨基保护及氯代得到1-乙氧甲酰基-4-哌啶甲酰氯(3),3与1,3-二氟苯经傅-克酰基化、脱氨基保护、肟化、环合、成盐得到6-氟-3-(4-哌啶基)-1,2-苯并异唑盐酸盐(7)。7和3-(2-氯乙基)-6,7,8,9-四氢-2-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮在碱催化下缩合得到利培酮(1)。结果与结论合成的利培酮经1H-NMR1、3C-NMR、MS确证结构,总收率21.5%。该合成工艺原料价廉易得、操作简便,适合工业化生产。
Aim To synthesize risperidone. Methods 4-Piperidinecarboxylic acid was used as starting material to give 1-ethoxycarbinyl-4-piperidinecarbonyl chloride （3） via protection and chlorination. 3 was treated with 1,3-difluorobenzene through Friedel-Crafts acylation, deprotection, oximation, cyclization and salt formation to generate the key intermediate 6-fluoro-3-（4-piperidinyl）-1, 2-benzisoxazole （7）, which was subjected to condensation with 3- （2- chloroethyl）-6, 7, 8, 9- tetrahydro-2-methyl-4 H-pyrido[ 1,2-a ] pyrimidin-4- one to afford risperidone. Results and conclusion The target compound was prepared with an overall yield of 21.5 % and its structure was identified by ^1H-NMR, ^13C-NMR and MS. In view of the cheap available materials and simple operations, this synthetic process is suitable for large-scale manufacture.
出处
《中国药物化学杂志》
CAS
CSCD
2007年第2期89-91,共3页
Chinese Journal of Medicinal Chemistry
关键词
工艺改进
利培酮
非典型抗精神病药物
process improvement
risperidone
atypical antipsychotic agent
