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【结 构 式】 
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【分子编号】55675 【品名】1-chloro-3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-2-propanol 【CA登记号】 |
【 分 子 式 】C15H21ClO3 【 分 子 量 】284.78264 【元素组成】C 63.26% H 7.43% Cl 12.45% O 16.85% |
合成路线1
该中间体在本合成路线中的序号：(IV)The condensation of 4-[2-(cyclopropylmethoxy)ethyl]phenol (I) with epichlorohydrin (II) in pyridine gives the phenol ether (III), which is treated with HCl to open the epoxide ring and yield the racemic chloropropanol (IV). The optical resolution of (IV) by means of Lipase SP 435-L or AK and vinyl acetate (V) gives a mixture of (S)-acetate (S)-(VI) and unreacted (R)-alcohol (R)-(VI) that is easily separated. Finally, the chiral chloropropanol (R)-(VI) is treated with isopropylamine (VII) to afford the target betaxolol. The optical resolution of racemic betaxolol by means of the previously mentioned lipases has also been tried with poor results.
| 【1】 Di Bono, G.; Scilimati, A.; Synthesis 1995, 6, 688. |
| 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) | 33330 | 4-[2-(Cyclopropylmethoxy)ethyl]phenol; p-(Cyclopropylmethoxyethyl)phenol | C12H16O2 | 详情 | 详情 | |
| (II) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (III) | 33331 | 2-([4-[2-(Cyclopropylmethoxy)ethyl]phenoxy]methyl)oxirane; 1-[p-(Cyclopropylmethoxyethyl)phenoxy]-2,3-epoxypropane; 4-[2-(Cyclopropylmethoxy)ethyl]phenyl 2-oxiranylmethyl ether | C15H20O3 | 详情 | 详情 | |
| (IV) | 55675 | 1-chloro-3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-2-propanol | C15H21ClO3 | 详情 | 详情 | |
| (V) | 24543 | vinyl acetate | 108-05-4 | C4H6O2 | 详情 | 详情 |
| (VI) | 55676 | (2R)-1-chloro-3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-2-propanol | C15H21ClO3 | 详情 | 详情 | |
| (VII) | 55676 | (2R)-1-chloro-3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-2-propanol | C15H21ClO3 | 详情 | 详情 | |
| (VIII) | 23933 | 2-Propanamine; Isopropylamine | 75-31-0 | C3H9N | 详情 | 详情 |