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【结 构 式】

【分子编号】48124

【品名】tert-butyl 4-methylene-1-piperidinecarboxylate

【CA登记号】

【 分 子 式 】C11H19NO2

【 分 子 量 】197.2774

【元素组成】C 66.97% H 9.71% N 7.1% O 16.22%

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:(I)

Treatment of piperidine (I) with 9-BBN in refluxing THF followed by reaction with bromo derivative (II) by means of K2CO3, PdCl2(dppf) and Ph3As in DMF/H2O provides chlorophenylsulfonyl derivative (III), whose Boc group is removed by means of TFA in CH2Cl2/H2O to afford secondary amine (IV). Reductive amination between amine (IV) and piperidone (V) by means of NaB(OAc)3H in CH2Cl2 in the presence of HOAc furnishes compound (VI), which is then deprotected by means of TFA in CH2Cl2/H2O to yield bipiperidinyl derivative (VII). Finally, coupling of (VII) with 2-amino-3-methyl benzoic acid (VIII) by means of HOBt, DIEA and EDCI in DMF provides the target product. Alternatively, the synthesis of intermediate (VII) can be performed as follows: Protection of the piperidine moiety of (IX) by means of trifluoroacetic anhydride in CH2Cl2 followed by treatment with methanesulfonic acid and dibromodimethylhydantoin (DBDMH) affords bromo derivative (X), whose trifluoroacetate moiety is then removed by reaction with K2CO3 in MeOH/H2O to give piperidine derivative (XI). Reductive amination between (XI) and piperidone (V) by means of NaB(OAc)3H in CH2Cl2 in the presence of HOAc furnishes compound (XII), which is condensed with 3-chlorbenzenesulfonyl fluoride (XIII) by means of BuLi in THF and finally treated with TFA in CH2Cl2/H2O for Boc removal to provide the intermediate chlorophenylsulfonyl derivative (VII).

1 Miller, M.W.; Clader, J.W.; McCombie, S.W.; Vice, S.F.; Kozlowski, J.A. (Schering Corp.); Muscarinic antagonists. WO 0121590 .
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) 48124 tert-butyl 4-methylene-1-piperidinecarboxylate C11H19NO2 详情 详情
(II) 48125 (4-bromophenyl)(3-chlorophenyl)dioxo-lambda(6)-sulfane; 4-bromophenyl 3-chlorophenyl sulfone C12H8BrClO2S 详情 详情
(III) 48126 tert-butyl 4-[4-[(3-chlorophenyl)sulfonyl]benzyl]-1-piperidinecarboxylate C23H28ClNO4S 详情 详情
(IV) 48127 3-chlorophenyl 4-(4-piperidinylmethyl)phenyl sulfone; 4-[4-[(3-chlorophenyl)sulfonyl]benzyl]piperidine C18H20ClNO2S 详情 详情
(V) 18620 tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone 79099-07-3 C10H17NO3 详情 详情
(VI) 48128   C28H37ClN2O4S 详情 详情
(VII) 48129   C23H29ClN2O2S 详情 详情
(VIII) 48130 2-amino-3-methylbenzoic acid 4389-45-1 C8H9NO2 详情 详情
(IX) 26225 4-benzylpiperidine 31252-42-3 C12H17N 详情 详情
(X) 48131 1-[4-(4-bromobenzyl)-1-piperidinyl]-2,2,2-trifluoro-1-ethanone C14H15BrF3NO 详情 详情
(XI) 48132 4-(4-bromobenzyl)piperidine C12H16BrN 详情 详情
(XII) 48133   C22H33BrN2O2 详情 详情
(XIII) 48134 3-chlorobenzenesulfonyl fluoride C6H4ClFO2S 详情 详情
Extended Information