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【结 构 式】

【分子编号】47837

【品名】(3S)-6-(benzyloxy)-1-hexen-3-ol

【CA登记号】

【 分 子 式 】C13H18O2

【 分 子 量 】206.28472

【元素组成】C 75.69% H 8.8% O 15.51%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VIII)

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:(VIII)

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
Extended Information