【结 构 式】 |
【分子编号】26736 【品名】1-(methylsulfonyl)-1,4,5,6-tetrahydro-3-pyridinyl trifluoromethanesulfonate 【CA登记号】 |
【 分 子 式 】C7H10F3NO5S2 【 分 子 量 】309.2873496 【元素组成】C 27.18% H 3.26% F 18.43% N 4.53% O 25.86% S 20.74% |
合成路线1
该中间体在本合成路线中的序号:(III)The acylation of 3-hydroxypiperidine with tosyl chloride followed by oxidation of the OH group with CrO3 and H2SO4 gives 1-tosylpiperidine-3-one (II), which is converted into the enol triflate (III) by reaction with LHMDS and PhN(SO2CF3)2 in THF. The condensation of (III) with 1-(tert-butoxycarbonyl)-2-vinylpiperidine (IV) by means of Pd(OAc)2 affords the diene (V), which is selectively deprotected with NaOH in methanol to afford the piperidine (VI). The condensation of (VI) with silylated methyl propenoate (VII) by means of triethylamine in dichloromethane gives the nonisolated intermediate (VIII) that cyclizes to the tetracyclic compound (IX) (as major isomer). The reaction of (IX) with HF and pyridine in refluxing dichloromethane affords the silylated tetracyclic ketone (X) (as major isomer), which is desilylated with KF, KHCO3 and H2O2 in refluxing methanol/THF providing the tetracyclic hydroxyketone (XI) (as major isomer), separated by column chromatography. Elimination of the OH group of (XI) with C6F5OC(S)-Cl, Bu3SnH and AIBN in refluxing benzdene yields the tetracyclic ketone (XII), which is finally reduced with LiAlH4 in THF.
【1】 Brosius, A.D.; et al.; Total synthesis of (+)-aloperine. Use of a nitrogen-bound silicon tether in a intramolecular diels - Alder reaction. J Am Chem Soc 1999, 121, 4, 700. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
17573 | N-Phenyltrifluoromethanesulfonimide; Trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]methanesulfonamide | 37595-74-7 | C8H5F6NO4S2 | 详情 | 详情 | |
(I) | 24255 | 3-piperidinol | 6859-99-0 | C5H11NO | 详情 | 详情 |
(II) | 26735 | 1-(methylsulfonyl)-3-piperidinone | C6H11NO3S | 详情 | 详情 | |
(III) | 26736 | 1-(methylsulfonyl)-1,4,5,6-tetrahydro-3-pyridinyl trifluoromethanesulfonate | C7H10F3NO5S2 | 详情 | 详情 | |
(IV) | 26737 | tert-butyl (2R)-2-vinyl-1-piperidinecarboxylate | C12H21NO2 | 详情 | 详情 | |
(V) | 26738 | tert-butyl (2R)-2-[(E)-2-[1-(methylsulfonyl)-1,4,5,6-tetrahydro-3-pyridinyl]ethenyl]-1-piperidinecarboxylate | C18H30N2O4S | 详情 | 详情 | |
(VI) | 26739 | 1-(methylsulfonyl)-5-[(E)-2-[(2R)piperidinyl]ethenyl]-1,2,3,4-tetrahydropyridine | C13H22N2O2S | 详情 | 详情 | |
(VII) | 26750 | methyl (E)-3-(dimethyl[[(trifluoromethyl)sulfonyl]oxy]silyl)-2-propenoate | C7H11F3O5SSi | 详情 | 详情 | |
(VIII) | 26741 | methyl (E)-3-[dimethyl((2R)-2-[(E)-2-[1-(methylsulfonyl)-1,4,5,6-tetrahydro-3-pyridinyl]ethenyl]piperidinyl)silyl]-2-propenoate | C19H32N2O4SSi | 详情 | 详情 | |
(IX) | 26742 | methyl (5aR,5bR,11aR,12S,12aS)-11,11-dimethyl-1-(methylsulfonyl)-1,2,3,4,5a,5b,6,7,8,9,11,11a,12,12a-tetradecahydropyrido[2',1':5,1][1,2]azasilolo[4,3-g]quinoline-12-carboxylate | C19H32N2O4SSi | 详情 | 详情 | |
(X) | 26743 | (1R,2S,9S,10R,17R)-17-[fluoro(dimethyl)silyl]-3-(methylsulfonyl)-3,15-diazatetracyclo[7.7.1.0(2,7).0(10,15)]heptadec-7-en-16-one | C18H29FN2O3SSi | 详情 | 详情 | |
(XI) | 26744 | (1R,2S,9R,10R,17R)-17-hydroxy-3-(methylsulfonyl)-3,15-diazatetracyclo[7.7.1.0(2,7).0(10,15)]heptadec-7-en-16-one | C16H24N2O4S | 详情 | 详情 | |
(XII) | 26745 | (1S,2S,9S,10R)-3-(methylsulfonyl)-3,15-diazatetracyclo[7.7.1.0(2,7).0(10,15)]heptadec-7-en-16-one | C16H24N2O3S | 详情 | 详情 |