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【结 构 式】 
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【分子编号】44106 【品名】2-fluoro-1-ethanol 【CA登记号】371-62-0 |
【 分 子 式 】C2H5FO 【 分 子 量 】64.0595032 【元素组成】C 37.5% H 7.87% F 29.66% O 24.98% |
合成路线1
该中间体在本合成路线中的序号：(I)2-Fluoroethanol (I) was oxidized under Swern conditions to afford 2-fluoroacetaldehyde (II), which was condensed with tert-butyl 3-nitropropionate (III), yielding the hydroxy ester (IV). Hydrogenation of the nitro group of (IV) over Raney nickel produced amine (V). Subsequent coupling of N-carbobenzoxy-L-valine (VI) with amine (V) in the presence of EDC and HOBt furnished amide (VII). The hydroxyl group of (VII) was then oxidized to the corresponding ketone (VIII) by using Dess-Martin periodinane. Finally, the tert-butyl ester was cleaved by treatment with trifluoroacetic acid.
| 【1】 Guastella, J.; Yang, W.; Cai, S.X.; Keana, J.F.W.; Drewe, J.A. (Cytovia, Inc.); Dipeptide apoptosis inhibitors and the use thereof. EP 1033910; US 6184210; WO 9918781 . |
| 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) | 44106 | 2-fluoro-1-ethanol | 371-62-0 | C2H5FO | 详情 | 详情 |
| (II) | 44107 | 2-fluoroacetaldehyde | C2H3FO | 详情 | 详情 | |
| (III) | 44108 | tert-butyl 3-nitropropanoate | C7H13NO4 | 详情 | 详情 | |
| (IV) | 44109 | tert-butyl 5-fluoro-4-hydroxy-3-nitropentanoate | C9H16FNO5 | 详情 | 详情 | |
| (V) | 44110 | tert-butyl 3-amino-5-fluoro-4-hydroxypentanoate | C9H18FNO3 | 详情 | 详情 | |
| (VI) | 18092 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutyric acid | C13H17NO4 | 详情 | 详情 | |
| (VII) | 44111 | tert-butyl 3-[((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)amino]-5-fluoro-4-hydroxypentanoate | C22H33FN2O6 | 详情 | 详情 | |
| (VIII) | 44112 | tert-butyl 3-[((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)amino]-5-fluoro-4-oxopentanoate | C22H31FN2O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Nucleophilic substitution of the dichloropyrimidine derivative (I) with 2-phenylvinylsulfonamide (II) in the presence of NaH in DMF affords the sulfonamido pyrimidine (III). The remaining chloro group of (III) is subsequently displaced with the sodium alkoxide derived from 2-fluoroethanol (IV) to provide the target fluoroethyl ether.
| 【1】 Harada, H.; Kazami, J.-I:; Watanuki, S.; Tsuzuki, R.; Yanagisawa, I.; Sudoh, K.; Tsukamoto, S.-I.; Tanaka, A.; Fujimori, A.; Ethenesulfonamide derivatives, a novel class of orally active endothelin-A receptor antagonists. Chem Pharm Bull 2001, 49, 5, 606. |
| 【2】 Harada, H.; Kazami, J.; Watanuki, S.; Tsuzuki, R.; Sudou, K.; Tanaka, A. (Yamanouchi Pharmaceutical Co., Ltd.); Arylethenesulfonamide derivs. and drug compsn. containing the same. EP 0882719; US 6083955; WO 9722595 . |
合成路线3
该中间体在本合成路线中的序号：(VII)Conjugate addition of 4-(trimethylsilyl)phenylmagnesium bromide (II) to anhydroecgonine methyl ester (I) afforded regioselectively the 2-beta-carbomethoxy-3-beta-aryl tropane (III). Iododesilylation of (III) using ICl or iodine in the presence of AgBF4 gave the iodophenyl derivative (IV). Hydrolysis of the ester function of (IV) in aqueous dioxan yielded the corresponding acid (V). Treatment of (V) with POCl3 provided the acid chloride (VI), which was finally condensed with 2-fluoroethanol (VII) to yield the title fluoroethyl ester.
| 【1】 Gu, X.-H.; et al.; Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 23, 3049. |
| 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) | 21118 | methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate | C10H15NO2 | 详情 | 详情 | |
| (II) | 50257 | bromo[4-(trimethylsilyl)phenyl]magnesium | C9H13BrMgSi | 详情 | 详情 | |
| (III) | 50258 | methyl (1R,2S,3S,5S)-8-methyl-3-[4-(trimethylsilyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate | C19H29NO2Si | 详情 | 详情 | |
| (IV) | 50259 | methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate | C16H20INO2 | 详情 | 详情 | |
| (V) | 50260 | (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid | C15H18INO2 | 详情 | 详情 | |
| (VI) | 50261 | (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl chloride | C15H17ClINO | 详情 | 详情 | |
| (VII) | 44106 | 2-fluoro-1-ethanol | 371-62-0 | C2H5FO | 详情 | 详情 |