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【结 构 式】 
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【分子编号】47836 【品名】(1S)-1-[3-(benzyloxy)propyl]-2-propenyl acetate 【CA登记号】 |
【 分 子 式 】C15H20O3 【 分 子 量 】248.322 【元素组成】C 72.55% H 8.12% O 19.33% |
合成路线1
该中间体在本合成路线中的序号：(VII)Aldehyde (II) was prepared by mono-benzylation of 1,4-butanediol (I) followed by Swern oxidation. Subsequent addition of ethynylmagnesium bromide (III) to the aldehyde function of (II) provided propargyl alcohol (IV). Kinetic resolution of the racemic alcohol (IV) by lipase-mediated acetylation in the presence of vinyl acetate produced a mixture of the (S)-acetate (V) and the unreacted (R)-alcohol (VI). The required (S)-propargyl acetate (V) was subjected to partial hydrogenation using Lindlar catalyst to furnish allyl acetate (VII), which was further hydrolyzed to the chiral alcohol (VIII). After protection of (VIII) as the silylated derivative (IX), reductive removal of the benzyl ether using lithium naphthalenide afforded the primary alcohol (X). This was then treated with methanesulfonyl chloride and triethylamine to give mesylate (XI). Ozonolysis of the double bond of (XI), followed by reductive work-up with dimethyl sulfide, yielded aldehyde (XII). This was reacted with hydroxylamine hydrochloride and Et3N in allyl alcohol (XIII) to produce the intermediate nitrone (XIV), which underwent simultaneous 1,3-dipolar cycloaddition to allyl alcohol to furnish the isoxazolopyridine (XV) as a mixture of three diastereoisomers. This mixture was then subjected to hydrogenolytic N-O bond fission, producing piperidine (XVI).
| 【1】 Ooi, H.e; et al.; A concise enantioselective synthesis of antimalarial febrifugine alkaloids. Org Lett 2001, 3, 6, 953. |
| 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) | 43160 | 1,4-butanediol;1,4-Dihydroxybutane;1,4-Butylene glycol;Tetramethylene glycol | 110-63-4 | C4H10O2 | 详情 | 详情 |
| (II) | 46170 | 4-(benzyloxy)butanal | C11H14O2 | 详情 | 详情 | |
| (III) | 17778 | ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium | 4301-14-8 | C2HBrMg | 详情 | 详情 |
| (IV) | 47833 | 6-(benzyloxy)-1-hexyn-3-ol | C13H16O2 | 详情 | 详情 | |
| (V) | 47834 | (1S)-1-[3-(benzyloxy)propyl]-2-propynyl acetate | C15H18O3 | 详情 | 详情 | |
| (VI) | 47835 | (3R)-6-(benzyloxy)-1-hexyn-3-ol | C13H16O2 | 详情 | 详情 | |
| (VII) | 47836 | (1S)-1-[3-(benzyloxy)propyl]-2-propenyl acetate | C15H20O3 | 详情 | 详情 | |
| (VIII) | 47837 | (3S)-6-(benzyloxy)-1-hexen-3-ol | C13H18O2 | 详情 | 详情 | |
| (IX) | 47838 | ([(1S)-1-[3-(benzyloxy)propyl]-2-propenyl]oxy)(tert-butyl)diphenylsilane; benzyl (4S)-4-[[tert-butyl(diphenyl)silyl]oxy]-5-hexenyl ether | C29H36O2Si | 详情 | 详情 | |
| (X) | 47839 | (4S)-4-[[tert-butyl(diphenyl)silyl]oxy]-5-hexen-1-ol | C22H30O2Si | 详情 | 详情 | |
| (XI) | 47840 | (4S)-4-[[tert-butyl(diphenyl)silyl]oxy]-5-hexenyl methanesulfonate | C23H32O4SSi | 详情 | 详情 | |
| (XII) | 47841 | (4S)-4-[[tert-butyl(diphenyl)silyl]oxy]-5-oxopentyl methanesulfonate | C22H30O5SSi | 详情 | 详情 | |
| (XIII) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
| (XIV) | 47842 | (5S)-5-[[tert-butyl(diphenyl)silyl]oxy]-2,3,4,5-tetrahydro-1-pyridiniumolate | C21H27NO2Si | 详情 | 详情 | |
| (XV) | 47843 | ((4S)-4-[[tert-butyl(diphenyl)silyl]oxy]hexahydro-2H-isoxazolo[2,3-a]pyridin-2-yl)methanol | C24H33NO3Si | 详情 | 详情 | |
| (XVI) | 47844 | 3-((3S)-3-[[tert-butyl(diphenyl)silyl]oxy]piperidinyl)-1,2-propanediol | C24H35NO3Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Aldehyde (II) was prepared by mono-benzylation of 1,4-butanediol (I) followed by Swern oxidation. Subsequent addition of ethynylmagnesium bromide (III) to the aldehyde function of (II) provided propargyl alcohol (IV). Kinetic resolution of the racemic alcohol (IV) by lipase-mediated acetylation in the presence of vinyl acetate produced a mixture of the (S)-acetate (V) and the unreacted (R)-alcohol (VI). The required (S)-propargyl acetate (V) was subjected to partial hydrogenation using Lindlar catalyst to furnish allyl acetate (VII), which was further hydrolyzed to the chiral alcohol (VIII). After protection of (VIII) as the silylated derivative (IX), reductive removal of the benzyl ether using lithium naphthalenide afforded the primary alcohol (X). This was then treated with methanesulfonyl chloride and triethylamine to give mesylate (XI). Ozonolysis of the double bond of (XI), followed by reductive work-up with dimethyl sulfide, yielded aldehyde (XII). This was reacted with hydroxylamine hydrochloride and Et3N in allyl alcohol (XIII) to produce the intermediate nitrone (XIV), which underwent simultaneous 1,3-dipolar cycloaddition to allyl alcohol to furnish the isoxazolopyridine (XV) as a mixture of three diastereoisomers. This mixture was then subjected to hydrogenolytic N-O bond fission, producing piperidine (XVI).
| 【1】 Ooi, H.e; et al.; A concise enantioselective synthesis of antimalarial febrifugine alkaloids. Org Lett 2001, 3, 6, 953. |
| 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) | 43160 | 1,4-butanediol;1,4-Dihydroxybutane;1,4-Butylene glycol;Tetramethylene glycol | 110-63-4 | C4H10O2 | 详情 | 详情 |
| (II) | 46170 | 4-(benzyloxy)butanal | C11H14O2 | 详情 | 详情 | |
| (III) | 17778 | ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium | 4301-14-8 | C2HBrMg | 详情 | 详情 |
| (IV) | 47833 | 6-(benzyloxy)-1-hexyn-3-ol | C13H16O2 | 详情 | 详情 | |
| (V) | 47834 | (1S)-1-[3-(benzyloxy)propyl]-2-propynyl acetate | C15H18O3 | 详情 | 详情 | |
| (VI) | 47835 | (3R)-6-(benzyloxy)-1-hexyn-3-ol | C13H16O2 | 详情 | 详情 | |
| (VII) | 47836 | (1S)-1-[3-(benzyloxy)propyl]-2-propenyl acetate | C15H20O3 | 详情 | 详情 | |
| (VIII) | 47837 | (3S)-6-(benzyloxy)-1-hexen-3-ol | C13H18O2 | 详情 | 详情 | |
| (IX) | 47838 | ([(1S)-1-[3-(benzyloxy)propyl]-2-propenyl]oxy)(tert-butyl)diphenylsilane; benzyl (4S)-4-[[tert-butyl(diphenyl)silyl]oxy]-5-hexenyl ether | C29H36O2Si | 详情 | 详情 | |
| (X) | 47839 | (4S)-4-[[tert-butyl(diphenyl)silyl]oxy]-5-hexen-1-ol | C22H30O2Si | 详情 | 详情 | |
| (XI) | 47840 | (4S)-4-[[tert-butyl(diphenyl)silyl]oxy]-5-hexenyl methanesulfonate | C23H32O4SSi | 详情 | 详情 | |
| (XII) | 47841 | (4S)-4-[[tert-butyl(diphenyl)silyl]oxy]-5-oxopentyl methanesulfonate | C22H30O5SSi | 详情 | 详情 | |
| (XIII) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
| (XIV) | 47842 | (5S)-5-[[tert-butyl(diphenyl)silyl]oxy]-2,3,4,5-tetrahydro-1-pyridiniumolate | C21H27NO2Si | 详情 | 详情 | |
| (XV) | 47843 | ((4S)-4-[[tert-butyl(diphenyl)silyl]oxy]hexahydro-2H-isoxazolo[2,3-a]pyridin-2-yl)methanol | C24H33NO3Si | 详情 | 详情 | |
| (XVI) | 47844 | 3-((3S)-3-[[tert-butyl(diphenyl)silyl]oxy]piperidinyl)-1,2-propanediol | C24H35NO3Si | 详情 | 详情 |