|
【结 构 式】 
|
【分子编号】46239 【品名】tert-butyl 1-[4-methoxy-3-(phenethyloxy)benzyl]-4-methylpentylcarbamate 【CA登记号】 |
【 分 子 式 】C27H39NO4 【 分 子 量 】441.611 【元素组成】C 73.43% H 8.9% N 3.17% O 14.49% |
合成路线1
该中间体在本合成路线中的序号：(VI)Wittig reaction between aldehyde (I) and bromo derivative (II) by means of triethyl phosphonoacetate and NaH in 1,2-dimethoxyethane (A) affords a mixture of isomeric acrylates (IIIa-b), which are hydrogenated over Pd/C in EtOH to yield derivative (IV). Hydrolysis of ethyl ester (IV) by means of KOH or NaOH provides carboxylic acid (V), which is then converted into N-protected derivative (VI) by first treatment with diphenylphosphoryl azide (DPPA) and Et3N in refluxing benzene, followed by reaction with refluxing t-butanol. Boc removal of (VI) with TFA in CH2Cl2 furnishes free amine (VII), which is finally alkylated with propyl bromide (VIII) by means of K2CO3 in DMF to yield the target product.
| 【1】 Tomisawa, K.; Ohta, K.; Nakazato, A.; Kumagai, T.; Chaki, S.; Okuyama, S.; Synthesis and SAR of 1-alkyl-2-phenylethylamine derivatives designed from N,N-dipropyl-4-methoxy-3-(2-phenylethoxy)phenylethylamine to discover sigma1 ligands. J Med Chem 1999, 42, 19, 3965. |
| 【2】 Nakazato, A.; Kumagai, T.; Miyazawa, T.; Ohta, K.; Kawashima, Y.; Hatayama, K. (Taisho Pharmaceutical Co., Ltd.); Optically active substd. phenylalkylamine derivs.. EP 0870758; JP 1997059230; US 5990151; WO 9700238 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (IIIa) | 46235 | ethyl (Z)-2-isopentyl-3-[4-methoxy-3-(phenethyloxy)phenyl]-2-propenoate | C25H32O4 | 详情 | 详情 | |
| (IIIb) | 46236 | ethyl (E)-2-isopentyl-3-[4-methoxy-3-(phenethyloxy)phenyl]-2-propenoate | C25H32O4 | 详情 | 详情 | |
| (I) | 23679 | 4-methoxy-3-(phenethyloxy)benzaldehyde | C16H16O3 | 详情 | 详情 | |
| (II) | 46234 | 1-bromo-3-methylbutane | C5H11Br | 详情 | 详情 | |
| (IV) | 46237 | ethyl 2-[4-methoxy-3-(phenethyloxy)benzyl]-5-methylhexanoate | C25H34O4 | 详情 | 详情 | |
| (V) | 46238 | 2-[4-methoxy-3-(phenethyloxy)benzyl]-5-methylhexanoic acid | C23H30O4 | 详情 | 详情 | |
| (VI) | 46239 | tert-butyl 1-[4-methoxy-3-(phenethyloxy)benzyl]-4-methylpentylcarbamate | C27H39NO4 | 详情 | 详情 | |
| (VII) | 46240 | 1-[4-methoxy-3-(phenethyloxy)benzyl]-4-methylpentylamine; 1-[4-methoxy-3-(phenethyloxy)phenyl]-5-methyl-2-hexanamine | C22H31NO2 | 详情 | 详情 | |
| (VIII) | 19502 | Propyl bromide; 1-Bromopropane | 106-94-5 | C3H7Br | 详情 | 详情 |