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【结 构 式】 
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【药物名称】BM-113 【化学名称】1-[2-(Benzhydryloxy)ethyl]piperidine-4-acetic acid ethyl ester 【CA登记号】115313-90-1, 115313-91-2 (maleate) 【 分 子 式 】C24H31NO3 【 分 子 量 】381.51957 |
【开发单位】Meram (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Histamine H1 Antagonists |
合成路线1
The title compound was obtained by two related procedures. Reaction of 4-piperidone-HCl (II) with 2-(benzhydryloxy)ethyl chloride (I) in the presence of Na2CO3 and NaI provided the N-alkylated piperidone (III). Horner-Emmons condensation of (III) with triethyl phosphonoacetate (IV) and NaH gave rise to the piperidylidene acetate (V). Then, hydrogenation of the double bond of (V) using Raney Nickel yielded the target compound.
| 【1】 Buzas, A.; Merour, J.-Y.; Ollivier, R. (Laboratoires Meram SA); Benzhydryloxyethylpiperidine derivs., process for their preparation and pharmaceutical compsns., in which they are present. EP 0259227; US 4983614 . |
| 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) | 34744 | 1-[(2-chloroethoxy)(phenyl)methyl]benzene; benzhydryl 2-chloroethyl ether | 32669-06-0 | C15H15ClO | 详情 | 详情 |
| (II) | 27115 | 4-piperidinone | 40064-34-4 | C5H9NO | 详情 | 详情 |
| (III) | 34745 | 1-[2-(benzhydryloxy)ethyl]-4-piperidinone | C20H23NO2 | 详情 | 详情 | |
| (IV) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (V) | 34746 | ethyl 2-[1-[2-(benzhydryloxy)ethyl]-4-piperidinylidene]acetate | C24H29NO3 | 详情 | 详情 |
合成路线2
Horner-Emmons condensation of 1-benzyl-4-piperidone (VI) with phosphonate (IV) furnished the unsaturated ester (VII). Hydrogenation of (VII) over Pd/C produced double bond reduction and simultaneous N-benzyl group cleavage to afford piperidine (VIII). This was finally alkylated with chloride (I) in the presence of K2CO3 and NaI.
| 【1】 Buzas, A.; Merour, J.-Y.; Ollivier, R. (Laboratoires Meram SA); Benzhydryloxyethylpiperidine derivs., process for their preparation and pharmaceutical compsns., in which they are present. EP 0259227; US 4983614 . |
| 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) | 34744 | 1-[(2-chloroethoxy)(phenyl)methyl]benzene; benzhydryl 2-chloroethyl ether | 32669-06-0 | C15H15ClO | 详情 | 详情 |
| (IV) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (VI) | 15720 | 1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one | 3612-20-2 | C12H15NO | 详情 | 详情 |
| (VII) | 34747 | ethyl 2-(1-benzyl-4-piperidinylidene)acetate | C16H21NO2 | 详情 | 详情 | |
| (VIII) | 28087 | 4-Piperidineacetic acid ethyl ester; ethyl 2-(4-piperidinyl)acetate | C9H17NO2 | 详情 | 详情 |