【结 构 式】 |
【分子编号】58485 【品名】benzyl 4-benzyl-4-hydroxy-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C20H23NO3 【 分 子 量 】325.40756 【元素组成】C 73.82% H 7.12% N 4.3% O 14.75% |
合成路线1
该中间体在本合成路线中的序号:(II)Acylation of 4-benzyl-4-hydroxypiperidine (I) by means of benzyl chloroformate provides carbamate (II). Subsequent dehydration of the tertiary alcohol group of (II) employing SOCl2 and pyridine leads to the tetrahydropyridine (III). Oxidation of tetrahydropyridine (III) with m-chloroperbenzoic acid gives epoxide (IV) which, upon acidic hydrolysis, is converted to the trans-diol (V). Resolution of the racemic diol (V) is performed via esterification with (S)-N-trifluoroacetylproline chloride (VI), followed by chromatographic separation of the resultant diastereomeric esters. The desired isomer (VII) is then hydrolyzed under basic conditions to yield the (R,R)-diol (VIII). Removal of the N-carbobenzoxy group of (VIII) by hydrogenolysis leads to (R,R)-4-benzyl-3,4-dihydroxypiperidine (IX), which is alkylated by the alkyl chloride (X) to produce (XI). Finally, hydrogenolysis of the benzyl ether group of (XI) furnishes the title compound.
【1】 Wyler, R.; Buettelmann, B.; Alanine, A.; Pinard, E.; Jaeschke, G.; Neidhart, M.-P. (Hoffmann-La Roche, Inc.); Neuroprotective substd. piperidine cpds. with activity as NMDA NR2B subtype selective antagonists. US 6432985; WO 0181309 . |
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) | 58484 | 4-benzyl-4-piperidinol; 4-Benzyl-4-hydroxypiperidine | 51135-96-7 | C12H17NO | 详情 | 详情 |
(II) | 58485 | benzyl 4-benzyl-4-hydroxy-1-piperidinecarboxylate | C20H23NO3 | 详情 | 详情 | |
(III) | 58486 | benzyl 4-benzyl-3,6-dihydro-1(2H)-pyridinecarboxylate | C20H21NO2 | 详情 | 详情 | |
(IV) | 58487 | benzyl 6-benzyl-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate | C20H21NO3 | 详情 | 详情 | |
(V) | 58488 | benzyl (3R,4R)-4-benzyl-3,4-dihydroxy-1-piperidinecarboxylate | C20H23NO4 | 详情 | 详情 | |
(VI) | 55850 | (5S)-5-(aminomethyl)-3-(4-{4-[2-(benzyloxy)acetyl]-1-piperazinyl}-3-fluorophenyl)-1,3-oxazolidin-2-one | C23H27FN4O4 | 详情 | 详情 | |
(VII) | 58489 | (2S)-1-(2,2,2-trifluoroacetyl)-2-pyrrolidinecarbonyl chloride | C7H7ClF3NO2 | 详情 | 详情 | |
(VIII) | 58490 | benzyl (3R,4R)-4-benzyl-4-hydroxy-3-({[(2S)-1-(2,2,2-trifluoroacetyl)pyrrolidinyl]carbonyl}oxy)-1-piperidinecarboxylate | C27H29F3N2O6 | 详情 | 详情 | |
(IX) | 58491 | (3R,4R)-4-benzyl-3,4-piperidinediol | C12H17NO2 | 详情 | 详情 | |
(X) | 58492 | 1-(benzyloxy)-4-(2-chloroethoxy)benzene; benzyl 4-(2-chloroethoxy)phenyl ether | C15H15ClO2 | 详情 | 详情 | |
(XI) | 58493 | (3R,4R)-4-benzyl-1-{2-[4-(benzyloxy)phenoxy]ethyl}-3,4-piperidinediol | C27H31NO4 | 详情 | 详情 |