ethyl 4-ethoxycyclohexanecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】25452

【品名】ethyl 4-ethoxycyclohexanecarboxylate

【CA登记号】

【分子式】C₁₁H₂₀O₃

【分子量】200.278

【元素组成】C 65.97% H 10.07% O 23.97%

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：(III)

Ethyl 4-hydroxybenzoate (I) was alkylated with EtI and K2CO3 to afford ethyl ether (II). Subsequent hydrogenation of (II) over Rh/C produced ethyl 4-ethoxycyclohexane carboxylate (III) (1). Then, alkylation of (III) using benzyl chloromethyl ether and LDA gave the benzyloxymethyl compound (IV), which was hydrolyzed with ethanolic KOH to the carboxylic acid (V). Coupling of N-Boc-L-phenylalanine (VI) with benzylamine in the presence of EDC and HOBt produced amide (VII), and further acid deprotection of the Boc group of (VII) yielded phenylalanine-N-benzylamide (VIII). This was coupled with carboxylic acid (V) by means of DCC and HOAt to provide diamide (IX), which was debenzylated by catalytic hydrogenation yielding alcohol (X).

参考文献中间体

合成目标

【1】 Fink, C.A.; et al.; Design and synthesis of thiol containing inhibitors of matrix metalloproteinases. Bioorg Med Chem Lett 1999, 9, 2, 195.
【2】 Fink, C.A. (Novartis AG); Certain cyclic thio substd. acylaminoacid amide derivs.. EP 0966439; US 6034136; WO 9842662 .

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)	13492	ethyl p-hydroxybenzoate; ethyl 4-hydroxybenzoate	120-47-8	C₉H₁₀O₃	详情	详情
(II)	25451	ethyl 4-ethoxybenzoate	23676-09-7	C₁₁H₁₄O₃	详情	详情
(III)	25452	ethyl 4-ethoxycyclohexanecarboxylate		C₁₁H₂₀O₃	详情	详情
(IV)	25453	ethyl 1-[(benzyloxy)methyl]-4-ethoxycyclohexanecarboxylate		C₁₉H₂₈O₄	详情	详情
(V)	25454	1-[(benzyloxy)methyl]-4-ethoxycyclohexanecarboxylic acid		C₁₇H₂₄O₄	详情	详情
(VI)	22184	(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid		C₁₄H₁₉NO₄	详情	详情
(VII)	25506	tert-butyl (1S)-1-benzyl-2-(benzylamino)-2-oxoethylcarbamate		C₂₁H₂₆N₂O₃	详情	详情
(VIII)	25507	(2S)-2-amino-N-benzyl-3-phenylpropanamide		C₁₆H₁₈N₂O	详情	详情
(IX)	25508	N-[(1S)-1-benzyl-2-(benzylamino)-2-oxoethyl]-1-[(benzyloxy)methyl]-4-ethoxycyclohexanecarboxamide		C₃₃H₄₀N₂O₄	详情	详情
(X)	25509	N-[(1S)-1-benzyl-2-(benzylamino)-2-oxoethyl]-4-ethoxy-1-(hydroxymethyl)cyclohexanecarboxamide		C₂₆H₃₄N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Ethyl 4-hydroxybenzoate (I) was alkylated with EtI and K2CO3 to afford ethyl ether (II). Subsequent hydrogenation of (II) over Rh/C produced ethyl 4-ethoxycyclohexane carboxylate (III) (1). Then, alkylation of (II) using benzyl chloromethyl ether and LDA gave the benzyloxymethyl compound (IV), which was hydrolyzed with ethanolic KOH to the carboxylic acid (V). Coupling of N-Boc-L-phenylalanine (VI) with 3-pyridylamine in the presence of EDC and HOBt produced amide (VII), and further acid deprotection of the Boc group of (VII) yielded phenylalanine-N-(3-pyridyl)amide (VIII). This was coupled with carboxylic acid (V) by means of DCC and HOAt to provide diamide (IX), which was debenzylated by catalytic hydrogenation yielding alcohol (X).

参考文献中间体

合成目标

【1】 Fink, C.A.; et al.; Design and synthesis of thiol containing inhibitors of matrix metalloproteinases. Bioorg Med Chem Lett 1999, 9, 2, 195.
【2】 Fink, C.A. (Novartis AG); Certain cyclic thio substd. acylaminoacid amide derivs.. EP 0966439; US 6034136; WO 9842662 .

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)	13492	ethyl p-hydroxybenzoate; ethyl 4-hydroxybenzoate	120-47-8	C₉H₁₀O₃	详情	详情
(II)	25451	ethyl 4-ethoxybenzoate	23676-09-7	C₁₁H₁₄O₃	详情	详情
(III)	25452	ethyl 4-ethoxycyclohexanecarboxylate		C₁₁H₂₀O₃	详情	详情
(IV)	25453	ethyl 1-[(benzyloxy)methyl]-4-ethoxycyclohexanecarboxylate		C₁₉H₂₈O₄	详情	详情
(V)	25454	1-[(benzyloxy)methyl]-4-ethoxycyclohexanecarboxylic acid		C₁₇H₂₄O₄	详情	详情
(VI)	22184	(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid		C₁₄H₁₉NO₄	详情	详情
(VII)	25455	tert-butyl (1S)-1-benzyl-2-oxo-2-(3-pyridinylamino)ethylcarbamate		C₁₉H₂₃N₃O₃	详情	详情
(VIII)	25456	(2S)-2-amino-3-phenyl-N-(3-pyridinyl)propanamide		C₁₄H₁₅N₃O	详情	详情
(IX)	25457	N-[(1S)-1-benzyl-2-oxo-2-(3-pyridinylamino)ethyl]-1-[(benzyloxy)methyl]-4-ethoxycyclohexanecarboxamide		C₃₁H₃₇N₃O₄	详情	详情
(X)	25458	N-[(1S)-1-benzyl-2-oxo-2-(3-pyridinylamino)ethyl]-4-ethoxy-1-(hydroxymethyl)cyclohexanecarboxamide		C₂₄H₃₁N₃O₄	详情	详情

Extended Information