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【结 构 式】

【分子编号】51259

【品名】benzyl (2R,3S)-3-hydroxy-2-(3-hydroxypropyl)-3,6-dihydro-1(2H)-pyridinecarboxylate

【CA登记号】

【 分 子 式 】C16H21NO4

【 分 子 量 】291.34708

【元素组成】C 65.96% H 7.27% N 4.81% O 21.97%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XVIII)

The dihydroxylation of 2-[3-(tert-butyldimethylsilyloxy)-1-propenyl]furan (I) with OsO4 and NMO gives the racemic diol (II), which is oxidized with MCPBA to yield the dhydropyranone (III). The cyclization of (III) by means of Ts-OH affords the racemic bicyclic enone (IV), which is reduced with NaBH4 to the racemic alcohol (V). The reaction of (V) with Ac2O and pyridine provides the racemic acetate (VI), which is treated with Lipase PS and vinyl acetate, furnishing a mixture of unreacted chiral acetate (-)-(VI) and the chiral alcohol (+)-(VII), which are easily separated. The reduction of (-)-(VII) with H2 over PtO2 gives the bicyclic alcohol (VIII), which is treated with Ms-Cl and TEA to yield the mesylate (IX). The reaction of (IX) with sodium azide in THF affords the azido derivative (X), which is reduced with LiAlH4 in THF to provide the bicyclic amine (XI). The protection of (XI) with benzyl chloroformate gives the carbamate (XII), which is alkylated with allyl bromide (XIII) and NaH in DMF to yield the N-allyl carbamate (XIV). The desilylation of (XIV) with TBAF, followed by a treatment with Ms-Cl and TEA, affords the mesylate (XV). The reaction of (XV) with LiI, and then reaction of the intermediate iodide with Zn/HOAc, provides the hemiacetal (XVI), which is further reduced with NaBH4 in ethanol to give the dihydroxydiene (XVII). The ring-closing metathesis reaction of (XVII) by means of Grubbs' catalyst yields the tetrahydropyridine (XVIII), which is reduced with H2 over PtO2 to afford the chiral dihydroxy piperidine (XIX). The reaction of (XIX) with diphenyl disulfide and tributyl phosphine provides the thioether (XX), which is treated with benzyl bromide and NaH to give the piperidin benzyl ether (XXI).

1 Taniguchi, T.; et al.; Lipase-mediated preparation of sugar building blocks. Synthesis 1999, 8, 1325.
2 Taniguchi, T.; Ofasawara, K.; A diastereocontrolled synthesis of (+)-febrifugine: A potent antimalarial piperidine alkaloid. Org Lett 2000, 2, 20, 3193.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(rac)-(VI) 51249 (rac)-7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]oct-3-en-2-yl acetate C15H26O5Si 详情 详情
(-)-(VI) 51263 (-)-7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]oct-3-en-2-yl acetate C15H26O5Si 详情 详情
(+)(VII) 65206 (+)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-6,8-dioxabicyclo[3.2.1]oct-3-en-2-ol C13H24O4Si 详情 详情
(I) 51244 tert-butyl(dimethyl)silyl (E)-3-(2-furyl)-2-propenyl ether; tert-butyl[[(E)-3-(2-furyl)-2-propenyl]oxy]dimethylsilane C13H22O2Si 详情 详情
(II) 51245 (1S,2R)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-(2-furyl)-1,2-propanediol C13H24O4Si 详情 详情
(III) 51246 (2S)-2-((1R)-2-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxyethyl)-6-hydroxy-2H-pyran-3(6H)-one C13H24O5Si 详情 详情
(IV) 51247 7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]oct-3-en-2-one C13H22O4Si 详情 详情
(V) 51248 (rac)-7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]oct-3-en-2-ol C13H24O4Si 详情 详情
(VIII) 51250 7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]octan-2-ol C13H26O4Si 详情 详情
(IX) 51251 7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]oct-2-yl methanesulfonate C14H28O6SSi 详情 详情
(X) 51252 [[(2S)-2-azido-6,8-dioxabicyclo[3.2.1]oct-7-yl]methoxy](tert-butyl)dimethylsilane; [(2S)-2-azido-6,8-dioxabicyclo[3.2.1]oct-7-yl]methyl tert-butyl(dimethyl)silyl ether C13H25N3O3Si 详情 详情
(XI) 51253 (2S)-7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]oct-2-ylamine; (2S)-7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]octan-2-amine C13H27NO3Si 详情 详情
(XII) 51254 benzyl (2S)-7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]oct-2-ylcarbamate C21H33NO5Si 详情 详情
(XIII) 11463 3-Bromo-1-propene; 3-Bromopropene;allyl bromide 106-95-6 C3H5Br 详情 详情
(XIV) 51255 benzyl allyl[(2S)-7-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6,8-dioxabicyclo[3.2.1]oct-2-yl]carbamate C24H37NO5Si 详情 详情
(XV) 51256 ((2S)-2-[allyl[(benzyloxy)carbonyl]amino]-6,8-dioxabicyclo[3.2.1]oct-7-yl)methyl methanesulfonate C19H25NO7S 详情 详情
(XVI) 51257 benzyl allyl[(2S,3R)-6-hydroxy-2-vinyltetrahydro-2H-pyran-3-yl]carbamate C18H23NO4 详情 详情
(XVII) 51258 benzyl allyl[(1R,2S)-2-hydroxy-1-(3-hydroxypropyl)-3-butenyl]carbamate C18H25NO4 详情 详情
(XVIII) 51259 benzyl (2R,3S)-3-hydroxy-2-(3-hydroxypropyl)-3,6-dihydro-1(2H)-pyridinecarboxylate C16H21NO4 详情 详情
(XIX) 51260 benzyl (2R,3S)-3-hydroxy-2-(3-hydroxypropyl)-1-piperidinecarboxylate C16H23NO4 详情 详情
(XX) 51261 benzyl (2R,3S)-3-hydroxy-2-[3-(phenylsulfanyl)propyl]-1-piperidinecarboxylate C22H27NO3S 详情 详情
(XXI) 51262 benzyl (2R,3S)-3-(benzyloxy)-2-[3-(phenylsulfanyl)propyl]-1-piperidinecarboxylate C29H33NO3S 详情 详情
Extended Information