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【结 构 式】 
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【分子编号】46917 【品名】(1S,5S,6R)-3-(4-fluorophenyl)-8-methyl-6-[(4-methylphenyl)sulfinyl]-8-azabicyclo[3.2.1]oct-3-en-2-one 【CA登记号】 |
【 分 子 式 】C21H20FNO2S 【 分 子 量 】369.4597432 【元素组成】C 68.27% H 5.46% F 5.14% N 3.79% O 8.66% S 8.68% |
合成路线1
该中间体在本合成路线中的序号：(IIIa),(IV)The dipolar cycloaddition of betaine (I) with (R)-p-tolyl vinyl sulfoxide (II) produced a mixture of exo and endo cycloadducts (III). Flash chromatography of the reaction mixture led to the separation of the exo tropenones as a diastereomeric mixture, and further crystallization from EtOAc provided the pure major isomer (IV). Copper-catalyzed conjugate addition of n-propylmagnesium bromide to the unsaturated ketone (IV) gave (V). The keto group was then reduced to alcohol (VI) using LiBH4. Tropane (VIII) was obtained by Barton deoxygenation of tropanol (VI) via conversion to thiono carbonate (VII) and subsequent reduction with Bu3SnH. Oxidation of the sulfoxide group to sulfone (IX) was carried out by means of oxone in aqueous MeOH. Fluorination with N-fluorobenzenesulfonimide gave the beta-fluoro compound (X). Finally, reductive desulfonation with sodium amalgam yielded the title compound.
| 【1】 Johnson, K.M.; Trzcinska, M.; Kozikowski, A.P.; Prakash, K.R.C.; An enantioselective synthesis and biobehavioral evaluation of 7-fluoro-3-(p-fluorophenyl)-2-propyltropanes. Bioorg Med Chem Lett 2000, 10, 13, 1443. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IIIa),(IV) | 46917 | (1S,5S,6R)-3-(4-fluorophenyl)-8-methyl-6-[(4-methylphenyl)sulfinyl]-8-azabicyclo[3.2.1]oct-3-en-2-one | C21H20FNO2S | 详情 | 详情 | |
| (IIIb) | 46918 | (1S,5S,6S)-3-(4-fluorophenyl)-8-methyl-6-[(4-methylphenyl)sulfinyl]-8-azabicyclo[3.2.1]oct-3-en-2-one | C21H20FNO2S | 详情 | 详情 | |
| (I) | 46916 | 4-(4-fluorophenyl)-1-methyl-3-pyridiniumolate | C12H10FNO | 详情 | 详情 | |
| (II) | 25801 | (4-methylphenyl)(oxo)vinyl-lambda(4)-sulfane; 4-methylphenyl vinyl sulfoxide | C9H10OS | 详情 | 详情 | |
| (V) | 46919 | (1S,4S,5S,6R)-3-(4-fluorophenyl)-8-methyl-6-[(4-methylphenyl)sulfinyl]-4-propyl-8-azabicyclo[3.2.1]octan-2-one | C24H28FNO2S | 详情 | 详情 | |
| (VI) | 46920 | (1S,2S,3R,4S,5S,6R)-3-(4-fluorophenyl)-8-methyl-6-[(4-methylphenyl)sulfinyl]-4-propyl-8-azabicyclo[3.2.1]octan-2-ol | C24H30FNO2S | 详情 | 详情 | |
| (VII) | 46921 | O-[(1S,2S,3R,4S,5S,6R)-3-(4-fluorophenyl)-8-methyl-6-[(4-methylphenyl)sulfinyl]-4-propyl-8-azabicyclo[3.2.1]oct-2-yl] O-phenyl carbonothioate | C31H34FNO3S2 | 详情 | 详情 | |
| (VIII) | 46922 | (1R,3R,4S,5S,6R)-3-(4-fluorophenyl)-8-methyl-4-propyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfoxide; (1S,2S,3R,5R,7R)-3-(4-fluorophenyl)-8-methyl-7-[(4-methylphenyl)sulfinyl]-2-propyl-8-azabicyclo[3.2.1]octane | C24H30FNOS | 详情 | 详情 | |
| (IX) | 46923 | (1S,2S,3R,5R,7R)-3-(4-fluorophenyl)-8-methyl-7-[(4-methylphenyl)sulfonyl]-2-propyl-8-azabicyclo[3.2.1]octane; (1R,3R,4S,5S,6R)-3-(4-fluorophenyl)-8-methyl-4-propyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfone | C24H30FNO2S | 详情 | 详情 | |
| (X) | 46924 | (1R,3R,4S,5S,6R)-6-fluoro-3-(4-fluorophenyl)-8-methyl-4-propyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfone; (1S,2S,3R,5R,7R)-7-fluoro-3-(4-fluorophenyl)-8-methyl-7-[(4-methylphenyl)sulfonyl]-2-propyl-8-azabicyclo[3.2.1]octane | C24H29F2NO2S | 详情 | 详情 |