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【结 构 式】 
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【分子编号】35909 【品名】ethyl 3-(diethoxyphosphoryl)propanoate 【CA登记号】3699-67-0 |
【 分 子 式 】C9H19O5P 【 分 子 量 】238.220622 【元素组成】C 45.38% H 8.04% O 33.58% P 13% |
合成路线1
该中间体在本合成路线中的序号：(XII)The condensation of (XI) with phosphonate (XII) by means of NaH in THF furnishes the unsaturated ester (XIII). The reduction of the double bond of (XIII) with H2 over Rh/Al2O3, followed by reduction of the ester group with DIBAL and oxidation of the resulting alcohol with DMP, gives rise to the aldehyde (XIV). The Wittig condensation of (XIV) with phosphonium salt (XV) by means of BuLi in THF yields the terminal olefin (XVI), which is selectively desilylated with Ts-OH to afford the primary alcohol (XVII). Finally, this compound is oxidized to the target carboxylic acid intermediate (XVIII) with DMP and NaClO2 in dichloromethane/THF.
| 【1】 Sinha, S.C.; Barbas, C.F. III; Lerner, R.A.; The antibody catalysis route to the total synthesis of epothilones. Proc Natl Acad Sci USA 1998, 95, 25, 14603. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 45549 | (3S,4S,5R,8S)-4,8,10-tris[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyl-6-oxodecanal | C32H68O5Si3 | 详情 | 详情 | |
| (XII) | 35909 | ethyl 3-(diethoxyphosphoryl)propanoate | 3699-67-0 | C9H19O5P | 详情 | 详情 |
| (XIII) | 45550 | ethyl (E,5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxo-2-dodecenoate | 2463-77-6 | C36H74O6Si3 | 详情 | 详情 |
| (XIV) | 45551 | (5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxododecanal | 94-59-7 | C34H72O5Si3 | 详情 | 详情 |
| (XV) | 13484 | Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide | 2065-66-9 | C19H18IP | 详情 | 详情 |
| (XVI) | 44436 | (5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-5-hexenyl]-4,12-dioxa-3,13-disilapentadecan-7-one | C35H74O4Si3 | 详情 | 详情 | |
| (XVII) | 44437 | (5S,8R,9S)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,11,11,12,12-undecamethyl-9-[(1S)-1-methyl-5-hexenyl]-4,10-dioxa-3,11-disilatridecan-7-one | C29H60O4Si2 | 详情 | 详情 | |
| (XVIII) | 44438 | (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid | C29H58O5Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXVI)The regiocontrolled condensation of the silylated propargyl aldehyde (LXI) with the chiral borane (LXII) gives the secondary alcohol (LXIII), which is silylated with TBDMS-OTf and lutidine in dichloromethane to the silyl ether (LXIV). The ozonolysis of the terminal double bond of (LXIV) with O3 in dichloromethane yields the aldehyde (LXV), which is condensed with the phosphonate (LXVI) by means of NaH in THF affording the unsaturated heptanoic ester (LXVII). The reduction of the ester group of (LXVII) with DIBAL in THF gives the alcohol (LXVIII), which is epoxidized with MCPBA as usual to the epoxide (LXIX). The condensation of (LXIX) with the Grignard reagent (LXX) in THF yields the diol (LXXI), which is selectively esterified with pivaloyl chloride affording the monopivalate (LXXII). The cyclic transketalization of (LXXII) catalyzed by HF in acetonitrile/water gives the cyclic ketal (LXXII), which is finally hydrolyzed by means of K2CO3 in methanol to provide the desired intermediate, the ethynyl derivative (LIX).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the novel immunosuppressant Sanglifehrin A. J Am Chem Soc 2000, 122, 16, 3830. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LIX) | 35903 | [(4S,6S)-3-ethynyl-1,4-dimethyl-2,9-dioxabicyclo[3.3.1]non-6-yl]methanol | C12H18O3 | 详情 | 详情 | |
| (LXI) | 35905 | 3-(triethylsilyl)-2-propynal | C9H16OSi | 详情 | 详情 | |
| (LXIII) | 35906 | (3R,4R)-4-methyl-1-(triethylsilyl)-5-hexen-1-yn-3-ol | C13H24OSi | 详情 | 详情 | |
| (LXIV) | 35907 | ((3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-hexen-1-ynyl)(triethyl)silane; tert-butyl(dimethyl)silyl (1R,2R)-2-methyl-1-[2-(triethylsilyl)ethynyl]-3-butenyl ether | C19H38OSi2 | 详情 | 详情 | |
| (LXV) | 35908 | (2S,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-5-(triethylsilyl)-4-pentynal | C18H36O2Si2 | 详情 | 详情 | |
| (LXVI) | 35909 | ethyl 3-(diethoxyphosphoryl)propanoate | 3699-67-0 | C9H19O5P | 详情 | 详情 |
| (LXVII) | 35910 | ethyl (E,4R,5R)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-7-(triethylsilyl)-2-hepten-6-ynoate | C22H42O3Si2 | 详情 | 详情 | |
| (LXVIII) | 35911 | (E,4R,5R)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-7-(triethylsilyl)-2-hepten-6-yn-1-ol | C20H40O2Si2 | 详情 | 详情 | |
| (LXIX) | 35912 | [3-[(1R,2R)-2-[[tert-butyl(dimethyl)silyl]oxy]-1-methyl-4-(triethylsilyl)-3-butynyl]-2-oxiranyl]methanol | C20H40O3Si2 | 详情 | 详情 | |
| (LXX) | 35913 | bromo[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]magnesium | C6H11BrMgO2 | 详情 | 详情 | |
| (LXXI) | 35914 | (2S,3S,4R,5R)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-2-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-7-(triethylsilyl)-6-heptyne-1,3-diol | C26H52O5Si2 | 详情 | 详情 | |
| (LXXII) | 35915 | (2S,3S,4R,5R)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-4-methyl-2-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-7-(triethylsilyl)-6-heptynyl pivalate | C31H60O6Si2 | 详情 | 详情 | |
| (LXXIII) | 35916 | [(4S,6S)-1,4-dimethyl-3-[2-(triethylsilyl)ethynyl]-2,9-dioxabicyclo[3.3.1]non-6-yl]methyl pivalate | C23H40O4Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IL)The condensation of (XLVIII) with phosphonate (XLIX) by means of NaH in THF furnishes the unsaturated ester (L). The reduction of the double bond of (L) with H2 over Rh/Al2O3, followed by reduction of the ester group with DIBAL and oxidation of the resulting alcohol with DMP, gives rise to the aldehyde (LI). The Wittig condensation of (LI) with phosphonium salt (LII) by means of BuLi in THF yields the terminal olefin (LIII), which is selectively desilylated with TsOH to afford the primary alcohol (LIV). Finally, this compound is oxidized to the target carboxylic acid intermediate (XII) with DMP and NaClO2 in dichloromethane/THF.
| 【1】 Sinha, S.C.; Barbas, C.F. III; Lerner, R.A.; The antibody catalysis route to the total synthesis of epothilones. Proc Natl Acad Sci USA 1998, 95, 25, 14603. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IL) | 35909 | ethyl 3-(diethoxyphosphoryl)propanoate | 3699-67-0 | C9H19O5P | 详情 | 详情 |
| (XII) | 44438 | (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid | C29H58O5Si2 | 详情 | 详情 | |
| (XLVIII) | 45549 | (3S,4S,5R,8S)-4,8,10-tris[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyl-6-oxodecanal | C32H68O5Si3 | 详情 | 详情 | |
| (L) | 45550 | ethyl (E,5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxo-2-dodecenoate | 2463-77-6 | C36H74O6Si3 | 详情 | 详情 |
| (LI) | 45551 | (5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxododecanal | 94-59-7 | C34H72O5Si3 | 详情 | 详情 |
| (LII) | 13484 | Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide | 2065-66-9 | C19H18IP | 详情 | 详情 |
| (LIII) | 44436 | (5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-5-hexenyl]-4,12-dioxa-3,13-disilapentadecan-7-one | C35H74O4Si3 | 详情 | 详情 | |
| (LIV) | 44437 | (5S,8R,9S)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,11,11,12,12-undecamethyl-9-[(1S)-1-methyl-5-hexenyl]-4,10-dioxa-3,11-disilatridecan-7-one | C29H60O4Si2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XII)The condensation of (XI) with phosphonate (XII) by means of NaH in THF furnishes the unsaturated ester (XIII). The reduction of the double bond of (XIII) with H2 over Rh/Al2O3, followed by reduction of the ester group with DIBAL and oxidation of the resulting alcohol with DMP, gives rise to the aldehyde (XIV). The Wittig condensation of (XIV) with phosphonium salt (XV) by means of BuLi in THF yields the terminal olefin (XVI), which is selectively desilylated with Ts-OH to afford the primary alcohol (XVII). Finally, this compound is oxidized to the target carboxylic acid intermediate (XVIII) with DMP and NaClO2 in dichloromethane/THF.
| 【1】 Sinha, S.C.; Barbas, C.F. III; Lerner, R.A.; The antibody catalysis route to the total synthesis of epothilones. Proc Natl Acad Sci USA 1998, 95, 25, 14603. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 45549 | (3S,4S,5R,8S)-4,8,10-tris[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyl-6-oxodecanal | C32H68O5Si3 | 详情 | 详情 | |
| (XII) | 35909 | ethyl 3-(diethoxyphosphoryl)propanoate | 3699-67-0 | C9H19O5P | 详情 | 详情 |
| (XIII) | 45550 | ethyl (E,5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxo-2-dodecenoate | 2463-77-6 | C36H74O6Si3 | 详情 | 详情 |
| (XIV) | 45551 | (5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxododecanal | 94-59-7 | C34H72O5Si3 | 详情 | 详情 |
| (XV) | 13484 | Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide | 2065-66-9 | C19H18IP | 详情 | 详情 |
| (XVI) | 44436 | (5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-5-hexenyl]-4,12-dioxa-3,13-disilapentadecan-7-one | C35H74O4Si3 | 详情 | 详情 | |
| (XVII) | 44437 | (5S,8R,9S)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,11,11,12,12-undecamethyl-9-[(1S)-1-methyl-5-hexenyl]-4,10-dioxa-3,11-disilatridecan-7-one | C29H60O4Si2 | 详情 | 详情 | |
| (XVIII) | 44438 | (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid | C29H58O5Si2 | 详情 | 详情 |