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【结 构 式】

【分子编号】69018

【品名】methyl 2-methyl-2-(4-(2-((methylsulfonyl)oxy)ethyl)phenyl)propanoate

【CA登记号】 

【 分 子 式 】C14H20O5S

【 分 子 量 】300.376

【元素组成】C 55.98% H 6.71% O 26.63% S 10.67%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XV)

Protection of 2-(4-piperidinyl)benzimidazole (I) with Boc2O in MeOH yields the N-Boc derivative (XI), which is then alkylated with 2-ethoxyethyl mesylate (XII) by means of KOH in toluene to afford the 1-(2-ethoxyethyl)benzimidazole (XIII). After deprotection of intermediate (XIII) with HCl in H2O, the resulting 1-(2-ethoxyethyl)-2-(4-piperidinyl)benzimidazole (X) is alkylated with mesylate (XIV) by means of Na2CO3 in refluxing MeOH, giving the ethyl ester (VIa).
Condensation of mesylate (XV) with 2-(4-piperidinyl)benzimidazole (I) by means of Na2CO3 in refluxing MeOH yields adduct (XVI), which is further alkylated with 2-ethoxyethyl mesylate (XII) in the presence of t-BuOK in DMF at 50 °C to afford the methyl ester (VIb) .

1 Lee, C.-H., Khoo, J.-H., Kwon, K.-C., Ju, H. (Yuhan Corp.). Process for preparation of 2-methyl-2’-phenylpropionic acid derivatives and novel intermediate compounds. WO 2009102155.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIa) 69008 ethyl 2-(4-(2-(4-(1-(2-ethoxyethyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)ethyl)phenyl)-2-methylpropanoate   C30H41N3O3 详情 详情
(VIb) 69009 methyl 2-(4-(2-(4-(1-(2-ethoxyethyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)ethyl)phenyl)-2-methylpropanoate   C29H39N3O3 详情 详情
(I) 54965 2-(4-piperidinyl)-1H-benzimidazole;2-(Piperidin-4-yl)benzimidazole;4-(Benzimidazol-2-yl)piperidine;2-Piperidin-4-yl-1H-benzimidazole 38385-95-4 C12H15N3 详情 详情
(X) 69012 1-(2-ethoxyethyl)-2-(4-piperidyl)benzimidazole;1-(2-ethoxyethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole   C16H23N3O 详情 详情
(XI) 69013 tert-butyl 4-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate   C17H23N3O2 详情 详情
(XII) 69014 2-ethoxyethyl mesylate;2-ethoxyethyl methanesulfonate   C5H12O4S 详情 详情
(XIII) 69015 tert-butyl 4-(1-(2-ethoxyethyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate   C21H31N3O3 详情 详情
(XIV) 69016 ethyl 2-methyl-2-(4-(2-((methylsulfonyl)oxy)ethyl)phenyl)propanoate   C15H22O5S 详情 详情
(XV) 69018 methyl 2-methyl-2-(4-(2-((methylsulfonyl)oxy)ethyl)phenyl)propanoate   C14H20O5S 详情 详情
(XVI) 69017 methyl 2-(4-(2-(4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)ethyl)phenyl)-2-methylpropanoate   C25H31N3O2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XV)

Coupling of 2-(4-bromophenyl)ethanol (XVII) with dimethylketene ethyl trimethylsilyl acetal (XVIIIa) in the presence of Pd(dba)2, (t-Bu)3P and ZnF2 in DMF at 80 °C gives the 2-arylisobutyrate ester (XIXa). Subsequent hydroxyl group sulfonylation in (XIXa) with MsCl and Et3N in CH2Cl2 yields the mesylate ester (XIV).
Similarly, 2-(4-bromophenyl)ethanol (XVII) (optionally pretreated with HMDS and NH4Cl in MeCN) is coupled with dimethylketene methyl trimethylsilyl acetal (XVIIIb) in the presence of Pd(dba)2, (t-Bu)3P and ZnF2 in DMF at 80 °C, giving 2-arylisobutyrate ester (XIXb), which is then sulfonylated with MsCl in the presence of Et3N in CH2Cl2, affording synthon (XV) .

1 Lee, C.-H., Khoo, J.-H., Kwon, K.-C., Ju, H. (Yuhan Corp.). Process for preparation of 2-methyl-2’-phenylpropionic acid derivatives and novel intermediate compounds. WO 2009102155.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XVIIIa) 44478 1-Ethoxy-2-methyl-1-trimethylsiloxypropene;1-Ethoxy-2-methyl-1-(trimethylsilyloxy)propene;1-Ethoxy-2-methyl-1-(trimethylsilyl)oxy-1-propene;1-ethoxy-2-methyl-1-propenyl trimethylsilyl ether; [(1-ethoxy-2-methyl-1-propenyl)oxy](trimethyl)silane ;dimethylketene ethyl trimethylsilyl acetal 31469-16-6 C9H20O2Si 详情 详情
(XVIIIb) 42016 1-Methoxy-2-methyl-1-(trimethylsiloxy)propene;1-Methoxy-2,2-dimethyl-1-(trimethylsiloxy)ethene;1-Methoxy-1-(trimethylsilyloxy)-2-methylpropene;[(1-methoxy-2-methyl-1-propenyl)oxy](trimethyl)silane; 1-methoxy-2-methyl-1-propenyl trimethylsilyl ether ;dimethylketene methyl trimethylsilyl acetal 31469-15-5 C8H18O2Si 详情 详情
(XIXa) 69019 ethyl 2-(4-(2-hydroxyethyl)phenyl)-2-methylpropanoate   C14H20O3 详情 详情
(XIXb) 69020 methyl 2-(4-(2-hydroxyethyl)phenyl)-2-methylpropanoate   C13H18O3 详情 详情
(XIV) 69016 ethyl 2-methyl-2-(4-(2-((methylsulfonyl)oxy)ethyl)phenyl)propanoate   C15H22O5S 详情 详情
(XV) 69018 methyl 2-methyl-2-(4-(2-((methylsulfonyl)oxy)ethyl)phenyl)propanoate   C14H20O5S 详情 详情
(XVII) 14248 2-(4-Bromophenyl)-1-ethanol; 4-Bromophenethyl alcohol;2-(4-bromophenyl)ethanol;2-(4-Bromophenyl)ethan-1-ol 4654-39-1 C8H9BrO 详情 详情
Extended Information