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1-二甲胺基-2-甲基-3-戊酮和间甲氧基苯基溴化镁经格氏反应制得1-二甲胺基-3-(3-甲氧基苯基)-2-甲基-3-戊醇盐酸盐(2),2用氯化亚砜氯代,经三溴化硼脱甲基得3-[3-氯-1-(二甲胺基)-2-甲基戊基-3-基]苯酚盐酸盐(4),4在4-叔丁基环己醇中用4-叔丁基环己醇钠顺式脱氯得去氢他喷他多(5),5与琥珀酸酐酯化得(Z)-3-[1-(二甲胺基)-2-甲基-2-戊烯-3-基)苯基丁二酸单酯(6),再经甲酯化、硼氢化钾还原、成盐得(Z)-3-[1-(二甲胺基)-2-甲基-2-戊烯-3-基]-苯基-4-羟丁酸酯琥珀酸盐(1),总收率31.8%。目标化合物为正在Ⅱ期临床试验的候选中枢性镇痛新药,命名为琥珀酸去氢他喷他多酯。
Dimethylamino-2-methyl-3-pentanone and m-methoxyphenylmagnesium bromide were subjected to Grignard reaction to prepare 1-dimethylamino-3- (3-methoxyphenyl) -2-methyl-3-pentanol hydrochloride (2), 2 was deprotected with boron tribromide using thionyl chloride to give 3- [3-chloro-1- (dimethylamino) Methylpentyl-3-yl] phenol hydrochloride (4), 4 cis-dechlorination with 4-tert-butylcyclohexanol in 4-tert- ), Esterification of 5 with succinic anhydride gave (Z) -3- [1- (dimethylamino) -2-methyl- Further methyl esterification and potassium borohydride reduction gave salts to give (Z) -3- [1- (dimethylamino) -2-methyl-2-penten-3-yl] -phenyl-4- Hydroxybutyrate succinate (1), total yield 31.8%. The target compound is a candidate central analgesic new drug in Phase II clinical trial, which is named Hydrastatadienol succinate.