【结 构 式】 |
【分子编号】16660 【品名】ethyl (2S)-2-[[(4-methylphenyl)sulfonyl]oxy]propanoate 【CA登记号】57057-80-4 |
【 分 子 式 】C12H16O5S 【 分 子 量 】272.32204 【元素组成】C 52.93% H 5.92% O 29.38% S 11.78% |
合成路线1
该中间体在本合成路线中的序号:(XIX)3) The tosylation of (S)-lactic acid ethyl ester (XVIII) with tosyl chloride and triethylamine gives the corresponding tosylate (XIX), which is reduced with NaBH4, diisobutylaluminum hydride (DIBAL) or borane.THF complex yielding 2(S)-(tosyloxy)-1-propanol (XX). The epoxidation of (XX) with KOH in water or NaH in DMSO/THF affords (R)-propylene oxide (XXI), which is condensed with 1-(benzyloxy)-2-propynyl (XXII) [obtained by benzylation of propargyl alcohol (XXIII) with benzyl chloride and NaOH] by means of butyllithium in THF or lithium amide in DMSO to give 6-benzyloxy-4-hexyn-2(R)-ol (XXIV). The acetylation of (XXIV) with acetic anhydride yields the corresponding acetate (XXV), which is reduced with H2 over Raney Nickel in ethanol to afford the expected 2(R),6-hexanediol derivative (XXVI). The debenzylation of (XXVI) by hydrogenation with H2 over Pd/C in acetic acid gives 5(R)-acetoxy-1-hexanol (XXVII), which is treated with SOCl2 to yield the corresponding hexyl chloride (XXVIII). The condensation of (XXVIII) with 3,7-dimethylxanthine (X) by means of sodium methoxide in DMSO affords the 5'-O-acetyllisofylline (XXIX), which is finally deacetylated by treatment with HCl in methanol/water. 4) The 5(R)-acetoxy-1-hexanol (XXVII) can also be obtained as follows: The addition of chiral epoxide (XXI) to acetaldehyde ethyl propargyl acetal (XXX) by means of lithium amide in DMSO gives 6-(1-ethoxyethoxy)-4-hexyn-2(R)-ol (XXXI), which is acetylated with acetic anhydride as before to the acetate (XXXII). The hydrogenation of (XXXII) with H2 over Raney Nickel in ethanol yields the corresponding saturated acetate (XXXIII), which is finally deprotected with aqueous HCl to the expected 5(R)-acetoxy-1-hexanol (XXVII) already reported.
【1】 Graul, J.; Casas, A.; Castañer, J.; Lisofylline. Drugs Fut 1997, 22, 5, 492. |
【2】 Klein, J.P.; Leigh, A.J.; Michnick, J.; Kumar, A.M.; Underiner, G.E. (Cell Therapeutics, Inc.); Asymetric synthesis of chiral secondary alcohols. WO 9531450 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(X) | 16651 | theobromine; 3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione | 83-67-0 | C7H8N4O2 | 详情 | 详情 |
(XVIII) | 16659 | ethyl (2S)-2-hydroxypropanoate; (S)-ethyl lactate | 687-47-8 | C5H10O3 | 详情 | 详情 |
(XIX) | 16660 | ethyl (2S)-2-[[(4-methylphenyl)sulfonyl]oxy]propanoate | 57057-80-4 | C12H16O5S | 详情 | 详情 |
(XX) | 16661 | (1S)-2-hydroxy-1-methylethyl 4-methylbenzenesulfonate | C10H14O4S | 详情 | 详情 | |
(XXI) | 16662 | (2R)-2-Methyloxirane; (R)-(+)-Propylene oxide | 15448-47-2 | C3H6O | 详情 | 详情 |
(XXII) | 16663 | benzyl 2-propynyl ether; 1-[(2-propynyloxy)methyl]benzene | C10H10O | 详情 | 详情 | |
(XXIII) | 16664 | Propargyl Alcohol; 2-propyn-1-ol | 107-19-7 | C3H4O | 详情 | 详情 |
(XXIV) | 16665 | (2R)-6-(benzyloxy)-4-hexyn-2-ol | C13H16O2 | 详情 | 详情 | |
(XXV) | 16666 | (1R)-5-(benzyloxy)-1-methyl-3-pentynyl acetate | C15H18O3 | 详情 | 详情 | |
(XXVI) | 16667 | (1R)-5-(benzyloxy)-1-methylpentyl acetate | C15H22O3 | 详情 | 详情 | |
(XXVII) | 16668 | (1R)-5-hydroxy-1-methylpentyl acetate | C8H16O3 | 详情 | 详情 | |
(XXVIII) | 16669 | (1R)-5-chloro-1-methylpentyl acetate | C8H15ClO2 | 详情 | 详情 | |
(XXIX) | 16670 | (1R)-5-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)-1-methylpentyl acetate | C15H22N4O4 | 详情 | 详情 | |
(XXX) | 16671 | 1-ethoxyethyl 2-propynyl ether; Acetaldehyde ethyl propargyl acetal; 3-(1-ethoxyethoxy)-1-propyne | 18669-04-0 | C7H12O2 | 详情 | 详情 |
(XXXI) | 16672 | (2R)-6-(1-ethoxyethoxy)-4-hexyn-2-ol | C10H18O3 | 详情 | 详情 | |
(XXXII) | 16673 | (1R)-5-(1-ethoxyethoxy)-1-methyl-3-pentynyl acetate | C12H20O4 | 详情 | 详情 | |
(XXXIII) | 16674 | (1R)-5-(1-ethoxyethoxy)-1-methylpentyl acetate | C12H24O4 | 详情 | 详情 |