methyl 2-methyl-2-(4-(2-((methylsulfonyl)oxy)ethyl)phenyl)propanoate -Drug Synthesis Database

【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 合成路线2

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) .

参考文献中间体

合成目标

【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) .

参考文献中间体

合成目标

【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