1-chloro-2-ethoxyethane -Drug Synthesis Database

【结构式】

【分子编号】29358

【品名】1-chloro-2-ethoxyethane

【CA登记号】628-34-2

【分子式】C₄H₉ClO

【分子量】108.56756

【元素组成】C 44.25% H 8.36% Cl 32.65% O 14.74%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The reaction of 2-chlorobenzimidazole (I) with 2-chloroethyl ethyl ether (II) by means of NaOH in DMF gives 1-(2-ethoxyethyl)benzimidazole (III), which is then condensed with N-methylhomopiperazine (IV) at 120 C.

参考文献中间体

合成目标

【1】 Iemura, R.; et al. (Kanebo Pharmaceuticals, Ltd.); Benzimidazole derivatives, process for the peparation thereof and pharmaceutical composition containing the same. EP 0079545; JP 58079983 .
【2】 Serradell, M.N.; Castaner, J.; KB-2413. Drugs Fut 1985, 10, 5, 397.

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)	26761	2-chloroimidazo[1,2-a]pyridine; 2-chlorobenzimidazole; 2-Amino-4'-chlorodiphenylether; 2-Aminodiphenylether; 2-chloro-1H-benzimidazole	4857-06-1	C₇H₅ClN₂	详情	详情
(II)	29358	1-chloro-2-ethoxyethane	628-34-2	C₄H₉ClO	详情	详情
(III)	20902	2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole; 2-(2-chloro-1H-benzimidazol-1-yl)ethyl ethyl ether		C₁₁H₁₃ClN₂O	详情	详情
(IV)	20903	1-methyl-1,4-diazepane	4318-37-0	C₆H₁₄N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Alkylation of piperidinylbenzimidazole (I) with tosylate (II) provided the N-substituted piperidine (III). The imidazole N of (III) was subsequently alkylated with 2-chloroethyl ethyl ether (IV) in the presence of NaH, yielding the N-ethoxyethyl derivative (V). Finally, the two-step, acid and basic, hydrolysis of the oxazoline ring of (V) furnished the title carboxylic acid.

参考文献中间体

合成目标

【1】 Orjales, A.; Rubio, V.; Bordell, M. (FAES); Benzimidazole derivs. with antihistaminic activity. EP 0818454; ES 2124167; JP 1998059961; US 5877187 .

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)	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
(II)	54966	4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl 4-methylbenzenesulfonate		C₂₃H₂₉NO₄S	详情	详情
(III)	54967	2-(1-{4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl}-4-piperidinyl)-1H-benzimidazole		C₂₈H₃₆N₄O	详情	详情
(IV)	29358	1-chloro-2-ethoxyethane	628-34-2	C₄H₉ClO	详情	详情
(V)	54968	2-[2-(1-{4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl}-4-piperidinyl)-1H-benzimidazol-1-yl]ethyl ethyl ether; 2-(1-{4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl}-4-piperidinyl)-1-(2-ethoxyethyl)-1H-benzimidazole		C₃₂H₄₄N₄O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

In the first strategy, alkylation of 2-(4-piperidinyl)-1H-benzimidazole (I) with the tosylate ester (II) in the presence of Na2CO3 in DMF at 80 °C provides the N-substituted piperidine (III), which is subsequently alkylated with 2-chloroethyl ethyl ether (IV) by means of NaH in DMF, yielding the N-ethoxyethyl derivative (V) . Finally, oxazolidinone (V) is submitted to acidic hydrolysis .
In the other strategy, saponification of propanoate esters (VIa) or (VIb) with NaOH in EtOH at 50-55 °C is followed by acidification with aqueous AcOH .

参考文献中间体

合成目标

【1】 Orjales, A., Rubio, V., Bordell, M. (FAES FARMA, SA). Benzimidazole derivatives with antihistaminic activity. EP 0818454, ES 2124167, JP 1998059961, US 5877187.
【2】 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
(II)	54966	4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl 4-methylbenzenesulfonate		C₂₃H₂₉NO₄S	详情	详情
(III)	54967	2-(1-{4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl}-4-piperidinyl)-1H-benzimidazole		C₂₈H₃₆N₄O	详情	详情
(IV)	29358	1-chloro-2-ethoxyethane	628-34-2	C₄H₉ClO	详情	详情
(V)	54968	2-[2-(1-{4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl}-4-piperidinyl)-1H-benzimidazol-1-yl]ethyl ethyl ether; 2-(1-{4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl}-4-piperidinyl)-1-(2-ethoxyethyl)-1H-benzimidazole		C₃₂H₄₄N₄O₂	详情	详情

Extended Information