【结 构 式】 |
【分子编号】45943 【品名】(2R,3R,4R,5R)-1,2,3,4,5-heptanepentol 【CA登记号】 |
【 分 子 式 】C7H16O5 【 分 子 量 】180.20104 【元素组成】C 46.66% H 8.95% O 44.39% |
合成路线1
该中间体在本合成路线中的序号:(I)The reaction of D-mannitol (I) with acetone and ZnCl2 gives the diacetonide (II), which is oxidized with Pb(OAc)4 to yield the acetonide of (R)-glyceraldehyde (III). The reduction of (III) with H2 over Pd/C affords the (S)-glycerin acetonide (IV), which is treated with TsCl in pyridine to provide the corresponding tosylate (V). The condensation of (V) with the urea derivative (VI) by means of KOH in DMSO gives the adduct (VII), which is deprotected with HCl in acetone to yield the diol (VIII). Monotosylation of (VIII) with TsCl in pyridine affords the primary tosylate (IX), which is treated with Na in methanol to provide the epoxide (X). Finally this compound is treated with tert-butylamine to furnish the target (R)-enantiomer.
【1】 Hofer, O.; Schlogl, K.; Absolute configuration and enantiomeric purity of celiprolol. Arzneim-Forsch Drug Res 1986, 36, 8, 1157. |
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) | 45943 | (2R,3R,4R,5R)-1,2,3,4,5-heptanepentol | C7H16O5 | 详情 | 详情 | |
(II) | 45944 | (1S,2S)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2-ethanediol | 1707-77-3 | C12H22O6 | 详情 | 详情 |
(III) | 36759 | (4R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde | 15186-48-8 | C6H10O3 | 详情 | 详情 |
(IV) | 12698 | [(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]methanol | 14347-78-5 | C6H12O3 | 详情 | 详情 |
(V) | 15208 | (S)-(+)-2,2-Dimethyl-4-(hydroxymethyl)-1,3-dioxolane-p-toluenesulfonate; [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate | 23735-43-5 | C13H18O5S | 详情 | 详情 |
(VI) | 33817 | N'-(3-acetyl-4-hydroxyphenyl)-N,N-diethylurea | C13H18N2O3 | 详情 | 详情 | |
(VII) | 45945 | N'-(3-acetyl-4-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]phenyl)-N,N-diethylurea | C19H28N2O5 | 详情 | 详情 | |
(VIII) | 45946 | N'-(3-acetyl-4-[[(2R)-2,3-dihydroxypropyl]oxy]phenyl)-N,N-diethylurea | C16H24N2O5 | 详情 | 详情 | |
(IX) | 45947 | (2S)-3-(2-acetyl-4-[[(diethylamino)carbonyl]amino]phenoxy)-2-hydroxypropyl 4-methylbenzenesulfonate | C23H30N2O7S | 详情 | 详情 | |
(X) | 45948 | N'-[3-acetyl-4-[(2R)oxiranylmethoxy]phenyl]-N,N-diethylurea | C16H22N2O4 | 详情 | 详情 | |
(XI) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |