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【结 构 式】

【分子编号】69382

【品名】(3-(aminomethyl)-2,2-dimethylcyclopropyl)methanol

【CA登记号】

【 分 子 式 】C7H15NO

【 分 子 量 】 129.20224

【元素组成】C 65.07% H 11.7% N 10.84% O 12.38%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(LVIII)

In a further process, the proline analogue (XI) is prepared starting from ethyl chrysanthemate (LV). Oxidative cleavage of the isobutenyl side-chain of compound (LV) with KMnO4 followed by alkaline hydrolysis of the ethyl ester group provides caronic acid (XLV) as a mixture of cis- and trans-isomers. Diacid (XLV) is then converted to the bicyclic anhydride (XLVI) using either trifluoroacetic anhydride or acetic anhydride as dehydrating reagents. Ring opening opening of anhydride (XLVI) with allyl alcohol and quinidine, followed by resolution with (R)-(+)-α-methylbenzylamine gives the chiral monoallyl ester (LVI), which is subsequently coupled with ammonium bicarbonate by means of di-tert-butyl dicarbonate and pyridine to afford the amide ester (LVII). After reduction of compound (LVII) with LiAlH4, the resulting amino alcohol (LVIII) is protected as the benzyl carbamate (LIX) by treatment with benzyl chloroformate and K2CO3. The primary alcohol (LIX) is then oxidized to aldehyde (LX) by means of sodium hypochlorite and a catalytic amount of TEMPO. Cyclization of aldehyde (LX) with AcOH in EtOH followed by replacement of the EtOH solvent with THF gives a mixture of the bicyclic hemiaminal (LXI) and its O-ethyl derivative (LXII), which, without separation, is treated with cyanotrimethylsilane and boron trifluoride etherate to afford nitrile (LXIII). Addition of NaOMe to the nitrile (LXIII) followed by aqueous hydrolysis of the obtained imidate (LXIV) provides ester (LXV), which can be alternatively obtained by treatment of nitrile (LXIII) with acetyl chloride in MeOH, followed by addition of water. Finally, the benzyl carbamate (LXV) is then deprotected by hydrogenation over Pd/C to yield the cyclopropanefused prolinate ester (XI) .

1 Park, J., Sudhakar, A., Wong, G.S. (Schering Corp.). Process and intermediates for the preparation of (1R,2S,5S)-6,6-dimethyl-3-azabicyclo-[3,1,0]hexane-2-carboxylates or salts thereof. JP 2007520434, US 2005059648, WO 2004113295.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XI) 69339 methyl (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate HCl salt 565456-77-1 C9H15NO2.HCl 详情 详情
(XLV) 69369 3,3-dimethylcyclopropane-1,2-dicarboxylic acid 497-42-7 C7H10O4 详情 详情
(XLVI) 69370 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione C7H8O3 详情 详情
(LV) 69379 Ethyl chrysanthemumate;ethyl 2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropanecarboxylate 97-41-6 C12H20O2 详情 详情
(LVI) 69380 3-((allyloxy)carbonyl)-2,2-dimethylcyclopropanecarboxylic acid C10H14O4 详情 详情
(LVII) 69381 allyl 3-carbamoyl-2,2-dimethylcyclopropanecarboxylate C10H15NO3 详情 详情
(LVIII) 69382 (3-(aminomethyl)-2,2-dimethylcyclopropyl)methanol C7H15NO 详情 详情
(LIX) 69383 benzyl ((3-(hydroxymethyl)-2,2-dimethylcyclopropyl)methyl)carbamate C15H21NO3 详情 详情
(LX) 69384 benzyl ((3-formyl-2,2-dimethylcyclopropyl)methyl)carbamate C15H19NO3 详情 详情
(LXI) 69385 benzyl 2-hydroxy-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carboxylate C15H19NO3 详情 详情
(LXII) 69386 benzyl 2-ethoxy-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carboxylate C17H23NO3 详情 详情
(LXIII) 69387 benzyl 2-cyano-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carboxylate C16H18N2O2 详情 详情
(LXIV) 69388 benzyl 2-(imino(methoxy)methyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carboxylate C17H22N2O3 详情 详情
(LXV) 69389 3-benzyl 2-methyl 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2,3-dicarboxylate C17H21NO4 详情 详情
Extended Information