• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】27665

【品名】phenyl (1R,2S,3R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate

【CA登记号】

【 分 子 式 】C27H27NO2

【 分 子 量 】397.51692

【元素组成】C 81.58% H 6.85% N 3.52% O 8.05%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XIV)

The reaction of tropanone (I) with N,N-bis(trifluoromethylsulfonyl)aniline and sodium hexamethyldisilylazide in THF gives the enol triflate (II), which is condensed with 4-methylphenylboronic acid (III) by means of palladium tetrakis(triphenylphosphine) yielding the p-tolyltropane (IV). The hydrolysis of the methyl ester of (IV) with KOH affords the carboxylic acid (V), which is treated with diphenoxyphosphoryl azide in hot toluene to give the isocyanate (VI). The hydrolysis of (VI) in refluxing ethanol yields the tropanone (VII), which by reaction with phenylmagnesium bromide in ethyl ether affords the diphenyltropanol (VIII). The dehydration of (VIII) with refluxing conc. HBr gives the diphenyltropene (XI), which by reaction with phenyl chloroformate in dichloromethane yields the N-carboxylate (XII). The reduction of (XII) with H2 over Pd/C in methanol affords a mixture of the (exo, exo) (XIII) and (endo, endo) (XIV) compounds, which is reduced with LiAlH4 in ethyl ether providing a mixture of the target compound and its (endo, endo) isomer (XV) that is separated by chromatography.

1 Jiang, S.; Chang, A.-C.; Abraham, P.; Kuhar, M.J.; Carroll, F.I.; Synthesis and transporter binding properties of (R)-2beta,3beta- and (R)-2alpha,3alpha-diaryltropanes. Bioorg Med Chem Lett 1998, 8, 24, 3689.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 27655 methyl (1R,5S)-8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate C10H15NO3 详情 详情
(II) 27656 methyl (1R,5S)-8-methyl-3-[[(trifluoromethyl)sulfonyl]oxy]-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate C11H14F3NO5S 详情 详情
(III) 15540 4-methylphenylboronic acid; p-Tolylboronic acid 5720-05-8 C7H9BO2 详情 详情
(IV) 27657 methyl (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate C17H21NO2 详情 详情
(V) 27658 (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid C16H19NO2 详情 详情
(VI) 27659 (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-en-2-yl isocyanate C16H18N2O 详情 详情
(VII) 27660 (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octan-2-one C15H19NO 详情 详情
(VIII) 27661 (1R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octan-2-ol C21H25NO 详情 详情
(XI) 27662 (1R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]oct-2-ene C21H23N 详情 详情
(XII) 27663 phenyl (1R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate C27H25NO2 详情 详情
(XIII) 27664 phenyl (1R,2R,3S,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate C27H27NO2 详情 详情
(XIV) 27665 phenyl (1R,2S,3R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate C27H27NO2 详情 详情
(XV) 27666 (1R,2S,3R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane C21H25N 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XIV)

The reaction of tropanone (I) with N,N-bis(trifluoromethylsulfonyl)aniline and sodium hexamethyldisilylazide in THF gives the enol triflate (II), which is condensed with 4-methylphenylboronic acid (III) by means of palladium tetrakis(triphenylphosphine) yielding the p-tolyltropane (IV). The hydrolysis of the methyl ester of (IV) with KOH affords the carboxylic acid (V), which is treated with diphenoxyphosphoryl azide in hot toluene to give the isocyanate (VI). The hydrolysis of (VI) in refluxing ethanol yields the tropanone (VII). By reaction of the tropanone (VII) with N,N-bis(trifluoromethylsulfonyl)aniline to give the corresponding enol triflate (IX), which is then condensed with phenylboronic acid (X) by means of Pd(Ph3)4 to give (XI), which by reaction with phenyl chloroformate in dichloromethane yields the N-carboxylate (XII). The reduction of (XII) with H2 over Pd/C in methanol affords a mixture of the (exo, exo) (XIII) and (endo, endo) (XIV) compounds, which is reduced with LiAlH4 in ethyl ether providing a mixture of the target compound and its (endo, endo) isomer (XV) that is separated by chromatography.

1 Jiang, S.; Chang, A.-C.; Abraham, P.; Kuhar, M.J.; Carroll, F.I.; Synthesis and transporter binding properties of (R)-2beta,3beta- and (R)-2alpha,3alpha-diaryltropanes. Bioorg Med Chem Lett 1998, 8, 24, 3689.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 27655 methyl (1R,5S)-8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate C10H15NO3 详情 详情
(II) 27656 methyl (1R,5S)-8-methyl-3-[[(trifluoromethyl)sulfonyl]oxy]-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate C11H14F3NO5S 详情 详情
(III) 15540 4-methylphenylboronic acid; p-Tolylboronic acid 5720-05-8 C7H9BO2 详情 详情
(IV) 27657 methyl (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate C17H21NO2 详情 详情
(V) 27658 (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid C16H19NO2 详情 详情
(VI) 27659 (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-en-2-yl isocyanate C16H18N2O 详情 详情
(VII) 27660 (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octan-2-one C15H19NO 详情 详情
(VIII) 27661 (1R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octan-2-ol C21H25NO 详情 详情
(IX) 27667 (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-en-2-yl trifluoromethanesulfonate C16H18F3NO3S 详情 详情
(X) 16593 Phenylboronic acid;Benzeneboronic acid;Phenylboron dihydroxide 98-80-6 C6H7BO2 详情 详情
(XI) 27662 (1R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]oct-2-ene C21H23N 详情 详情
(XII) 27663 phenyl (1R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate C27H25NO2 详情 详情
(XIII) 27664 phenyl (1R,2R,3S,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate C27H27NO2 详情 详情
(XIV) 27665 phenyl (1R,2S,3R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate C27H27NO2 详情 详情
(XV) 27666 (1R,2S,3R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane C21H25N 详情 详情
Extended Information