|
【结 构 式】 
|
【分子编号】50994 【品名】methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate 【CA登记号】 |
【 分 子 式 】C16H21NO2 【 分 子 量 】259.34828 【元素组成】C 74.1% H 8.16% N 5.4% O 12.34% |
合成路线1
该中间体在本合成路线中的序号：(V)Conjugate addition of tolylmagnesium bromide (II) to ecgonidine methyl ester (I) provided the 3-beta-tolyl tropane derivative (III). N-Dealkylation of (III) to produce the nortropane analogue (V) was carried out via acylation with trichloroethyl chloroformate, followed by reductive cleavage of the resultant trichloroethyl carbamate (IV) with Zn and HOAc. Alkylation of the secondary amine (V) with propargyl bromide (VI) afforded the corresponding propargyl amine (VII). Subsequent hydrostannylation of the propargyl group furnished the desired (E)-stannylpropenyl compound (VIII) along with the corresponding (Z)-isomer. In an improved procedure, amine (V) was alkylated with (E)-3-chloro-1-(tributylstannyl)-1-propene (IX) to yield pure (VIII). Finally, the title vinyl iodide was obtained by iododestannylation of (VIII) employing iodine in cold CHCl3.
| 【1】 Emond, P.; et al.; Synthesis and ligand bindin of nortropane derivatives: N-substituted 2beta-carbomethoxy-3beta-(4'-iodophenyl)nortropane and N-(3-iodotrop-(2E)-enyl)-2beta-carbomethoxy-3beta-(3',4'-disubstituted phenyl)nortropane. New high-affinity and selective compounds. J Med Chem 1997, 40, 9, 1366. |
| 【2】 Mauclaire, L.; Edmond, P.; Guilloteau, D.; Besnard, J.-C.; Frangin, Y. (CIS Bio International); Tropane derivs. useable in particular for in vivo detection of dopamine transporters. EP 0901491; JP 2000510141; US 6180083; WO 9743285 . |
| 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) | 21118 | methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate | C10H15NO2 | 详情 | 详情 | |
| (II) | 35657 | bromo(4-methylphenyl)magnesium | 4294-57-9 | C7H7BrMg | 详情 | 详情 |
| (III) | 50267 | methyl (1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C17H23NO2 | 详情 | 详情 | |
| (IV) | 50993 | 2-methyl 8-(2,2,2-trichloroethyl) (1R,2S,3S,5S)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate | C19H22Cl3NO4 | 详情 | 详情 | |
| (V) | 50994 | methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C16H21NO2 | 详情 | 详情 | |
| (VI) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (VII) | 50995 | tributyl[(E)-3-chloro-1-propenyl]stannane | C15H31ClSn | 详情 | 详情 | |
| (VIII) | 50996 | methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-(2-propynyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C19H23NO2 | 详情 | 详情 | |
| (IX) | 50997 | methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-[(E)-3-(tributylstannyl)-2-propenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate | C31H51NO2Sn | 详情 | 详情 |