【结 构 式】 |
【分子编号】14748 【品名】2-[2-(2-Chloroethoxy)ethoxy]-1-ethanol; 2-(2-(2-Chloroethoxy)ethoxy)ethanol 【CA登记号】5197-62-6 |
【 分 子 式 】C6H13ClO3 【 分 子 量 】168.62012 【元素组成】C 42.74% H 7.77% Cl 21.03% O 28.47% |
合成路线1
该中间体在本合成路线中的序号:(VI)The starting compound phthalimido derivative (I) could be obtained as follows: The condensation of 2-[2-(2-chloroethoxy)ethoxy]ethanol (VI) with potassium phthalimide (VII) in refluxing DMF gives the expected phthalimido derivative (VIII), which is oxidized with the Jones reagent in acetone yielding 2-[2-(2-phthalimidoethoxy)ethoxy]acetic acid (IX). The condensation of (IX) with 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) (X) by means of carbonyldiimidazole (CDI) and pyridine in dichloromethane affords 2,2-dimethyl-5-[2-[2-(2-phthalimidoethoxy)ethoxy]acetyl]-1,3-dioxane-4,6-dione (XI), which is finally treated with refluxing ethanol to obtain the phthalimido derivative (I) used as starting material.
【1】 Crouzel, C.; Duval, R.; Hinnen, F.; Fuseau, C.; Dollé, F.; Valette, H.; Péglion, J.-L.; Synthesis of two optically active calcium channel antagonists labelled with carbon-11 for in vivo cardiac PET imaging. Bioorg Med Chem 1997, 5, 4, 749. |
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) | 14743 | ethyl 4-[2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]ethoxy]-3-oxobutanoate | C18H21NO7 | 详情 | 详情 | |
(VI) | 14748 | 2-[2-(2-Chloroethoxy)ethoxy]-1-ethanol; 2-(2-(2-Chloroethoxy)ethoxy)ethanol | 5197-62-6 | C6H13ClO3 | 详情 | 详情 |
(VII) | 10926 | (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium | C8H4KNO2 | 详情 | 详情 | |
(VIII) | 14750 | 2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethyl]-1H-isoindole-1,3(2H)-dione | C14H17NO5 | 详情 | 详情 | |
(IX) | 14751 | 2-[2-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]ethoxy]acetic acid | C14H15NO6 | 详情 | 详情 | |
(X) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione;Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
(XI) | 14752 | 2-(2-[2-[2-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-2-oxoethoxy]ethoxy]ethyl)-1H-isoindole-1,3(2H)-dione | C20H21NO9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(II)Condensation of galactose pentaacetate (I) with 2-[2-(2-chloroethoxy)ethoxy]ethanol (II) in the presence of boron trifluoride etherate afforded the galactopyranoside (III). Subsequent hydrolysis of the acetate esters of (III) to give (IV) was carried out employing K2CO3 in MeOH. The galactose 3-hydroxyl group of (IV) was selectively protected as the p-methoxybenzyl ether (VI) by treatment with p-methoxybenzyl chloride (V) in the presence of dibutyltin oxide. After acetylation of the remaining free hydroxyl groups of (VII) to give (VIII), oxidative cleavage of its p-methoxybenzyl ether by means of cerium ammonium nitrate afforded the 2,4,6-triacetylated pyranoside (VIII). This was condensed with the galactose thioglycoside (IX) in the presence of methyl triflate to furnish the protected disaccharide (X). The benzyl protecting groups of (X) were then removed by hydrogenolysis yielding (XI).
【1】 Yu, L.; Jack, R.M.; Jones, D. (La Jolla Pharmaceutical Co.); Conjugates comprising galactose alpha 1,3 galactosyl epitopes and methods of using same. EP 1137652; WO 0034296 . |
【2】 Jones, D.S.; Engle, S.B.; Yu, L.; Jack, R.M. (La Jolla Pharmaceutical Co.); Methods and formulations for reducing circulating antibodies. WO 0033887 . |
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) | 52047 | [(2R,3S,4S,5R,6R)-3,4,5,6-tetrakis(acetoxy)tetrahydro-2H-pyran-2-yl]methyl acetate | C16H22O11 | 详情 | 详情 | |
(II) | 14748 | 2-[2-(2-Chloroethoxy)ethoxy]-1-ethanol; 2-(2-(2-Chloroethoxy)ethoxy)ethanol | 5197-62-6 | C6H13ClO3 | 详情 | 详情 |
(III) | 52048 | (2R,3S,4S,5R,6S)-3,5-bis(acetoxy)-2-[(acetoxy)methyl]-6-[2-[2-(2-chloroethoxy)ethoxy]ethoxy]tetrahydro-2H-pyran-4-yl acetate | C20H31ClO12 | 详情 | 详情 | |
(IV) | 52049 | (2S,3R,4S,5R,6R)-2-[2-[2-(2-chloroethoxy)ethoxy]ethoxy]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol | C12H23ClO8 | 详情 | 详情 | |
(V) | 11910 | 4-Methoxybenzyl chloride; 1-(Chloromethyl)-4-methoxybenzene; alpha-Chloro-4-methoxytoluene; 4-(Chloromethyl)phenyl methyl ether | 824-94-2 | C8H9ClO | 详情 | 详情 |
(VI) | 52050 | (2S,3R,4S,5R,6R)-2-[2-[2-(2-chloroethoxy)ethoxy]ethoxy]-6-(hydroxymethyl)-4-[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3,5-diol | C20H31ClO9 | 详情 | 详情 | |
(VII) | 52051 | (2R,3R,4S,5R,6S)-5-(acetoxy)-2-[(acetoxy)methyl]-6-[2-[2-(2-chloroethoxy)ethoxy]ethoxy]-4-[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl acetate | C26H37ClO12 | 详情 | 详情 | |
(VIII) | 52052 | (2R,3R,4S,5R,6S)-5-(acetoxy)-2-[(acetoxy)methyl]-6-[2-[2-(2-chloroethoxy)ethoxy]ethoxy]-4-hydroxytetrahydro-2H-pyran-3-yl acetate | C18H29ClO11 | 详情 | 详情 | |
(IX) | 52053 | benzyl (2R,3R,4S,5R,6R)-3,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-(methylsulfanyl)tetrahydro-2H-pyran-4-yl ether; (2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-2-[(benzyloxy)methyl]-6-(methylsulfanyl)tetrahydro-2H-pyran | C35H38O5S | 详情 | 详情 | |
(X) | 52054 | (2R,3S,4S,5R,6S)-5-(acetoxy)-2-[(acetoxy)methyl]-6-[2-[2-(2-chloroethoxy)ethoxy]ethoxy]-4-([(2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]oxy)tetrahydro-2H-pyran-3-yl acetate | C52H63ClO16 | 详情 | 详情 | |
(XI) | 52055 | (2R,3S,4S,5R,6S)-5-(acetoxy)-2-[(acetoxy)methyl]-6-[2-[2-(2-chloroethoxy)ethoxy]ethoxy]-4-[[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]tetrahydro-2H-pyran-3-yl acetate | C24H39ClO16 | 详情 | 详情 |