Ethyl 2-(4-hydroxyphenyl)acetate -Drug Synthesis Database

【结构式】

【分子编号】24994

【品名】Ethyl 2-(4-hydroxyphenyl)acetate

【CA登记号】17138-28-2

【分子式】C₁₀H₁₂O₃

【分子量】180.20348

【元素组成】C 66.65% H 6.71% O 26.64%

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：(I)

The condensation of ethyl p-hydroxyphenylacetate (I) with benzyl chloride (II) by means of sodium ethoxide in refluxing ethanol gives ethyl p-(benzyloxy)phenylacetate (III), which is reduced with LiAlH4 in THF to 2-(p-benzyloxyphenyl)ethanol (IV). The etherification of (IV) with cyclopropyl bromide (A) by means of NaH in hot DMF affords 4-(cyclopropylmethoxyethyl)-1-benzyloxybenzene (V), which is debenzylated by hydrogenation with H2 and Pd/C in methanol giving rise to p-(cyclopropylmethoxyethyl)phenol (VI). The condensation of (VI) with epichlorohydrin (B) by means of NaOH in water yields 1-[p-(cyclopropylmethoxyethyl)phenoxy]-2,3-epoxypropane (VII), which is treated with isopropylamine (C) and finally with HCl in ether.

参考文献中间体

合成目标

【1】 Manoury, P.M.J.; et al. (Sanofi-Synthelabo ); Phenol ethers. DE 2649605; FR 2330383; GB 1515978; JP 52085146; US 4252984 .
【2】 Hillier, K.; Castaner, J.; Serradell, M.N.; Blancafort, P.; Betaxolol hydrochloride. Drugs Fut 1979, 4, 12, 867.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(A)	22277	Cyclopropyl bromide; 1-(Bromomethyl)cyclopropane	7051-34-5	C₄H₇Br	详情	详情
(I)	24994	Ethyl 2-(4-hydroxyphenyl)acetate	17138-28-2	C₁₀H₁₂O₃	详情	详情
(II)	19171	1-(Chloromethyl)benzene; Benzyl chloride	100-44-7	C₇H₇Cl	详情	详情
(III)	28637	Ethyl 2-[4-(benzyloxy)phenyl]acetate; p-(Benzyloxy)phenylacetate		C₁₇H₁₈O₃	详情	详情
(IV)	33328	2-(p-Benzyloxyphenyl)ethanol; 2-[4-(Benzyloxy)phenyl]-1-ethanol		C₁₅H₁₆O₂	详情	详情
(V)	33329	4-(Cyclopropylmethoxyethyl)-1-benzyloxybenzene; 1-(Benzyloxy)-4-[2-(cyclopropylmethoxy)ethyl]benzene; Benzyl 4-[2-(cyclopropylmethoxy)ethyl]phenyl ether		C₁₉H₂₂O₂	详情	详情
(VI)	33330	4-[2-(Cyclopropylmethoxy)ethyl]phenol; p-(Cyclopropylmethoxyethyl)phenol		C₁₂H₁₆O₂	详情	详情
(VII)	33331	2-([4-[2-(Cyclopropylmethoxy)ethyl]phenoxy]methyl)oxirane; 1-[p-(Cyclopropylmethoxyethyl)phenoxy]-2,3-epoxypropane; 4-[2-(Cyclopropylmethoxy)ethyl]phenyl 2-oxiranylmethyl ether		C₁₅H₂₀O₃	详情	详情
(C)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

A new synthesis of 2-[4-[1-(tert-butoxycarbonyl)pyrrolidin-3(S)-yloxy)phenyl]-3-(7-cyano-2-naphthyl)-2-propenoic acid ethyl ester (VI), a key intermediate in the synthesis of DX-9065a has been described: The condensation of 3(R)-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester (I) with 4-hydroxyphenylacetic acid ethyl ester (II) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF gives 4-[1-(tert-butoxycarbonyl)pyrrolidin-3(R)-yloxy]phenylacetic acid ethyl ester (III), which is treated with formaldehyde, K2CO3 and tetrabutylammonium iodide in hot toluene yielding 2-[4-[1-(tert-butoxycarbonyl)pyrrolidin-3(R)-yloxy]phenyl]-2-propenoic acid ethyl ester (IV). Finally, this compound is condensed with 7-(trifluoromethylsulfonyloxy)naphthalene-2-carbonitrile (V) by means a Pd catalyst in hot DMF to afford the target compound (VI).

参考文献中间体

合成目标

【1】 Yokoyama, Y.; Synthesis of specific factor Xa inhibitor, DX-9065a. Symp Med Chem 1998, Abst L-15.

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)	16286	tert-butyl (3S)-3-hydroxytetrahydro-1H-pyrrole-1-carboxylate		C₉H₁₇NO₃	详情	详情
(II)	24994	Ethyl 2-(4-hydroxyphenyl)acetate	17138-28-2	C₁₀H₁₂O₃	详情	详情
(III)	24989	tert-butyl (3S)-3-[4-(2-ethoxy-2-oxoethyl)phenoxy]-1-pyrrolidinecarboxylate		C₁₉H₂₇NO₅	详情	详情
(IV)	24996	tert-butyl (3S)-3-[4-[1-(ethoxycarbonyl)vinyl]phenoxy]-1-pyrrolidinecarboxylate		C₂₀H₂₇NO₅	详情	详情
(V)	24997	7-cyano-2-naphthyl trifluoromethanesulfonate		C₁₂H₆F₃NO₃S	详情	详情
(VI)	16290	tert-butyl (3S)-3-[4-[(Z)-2-(7-cyano-2-naphthyl)-1-(ethoxycarbonyl)ethenyl]phenoxy]-1-pyrrolidinecarboxylate		C₃₁H₃₂N₂O₅	详情	详情
(VII)	24999	7-methoxy-3,4-dihydro-2(1H)-naphthalenone	4133-34-0	C₁₁H₁₂O₂	详情	详情
(VIII)	25000	7-methoxy-3,4-dihydro-2-naphthalenecarbonitrile		C₁₂H₁₁NO	详情	详情
(IX)	25001	7-methoxy-2-naphthonitrile		C₁₂H₉NO	详情	详情
(X)	25002	7-hydroxy-2-naphthonitrile		C₁₁H₇NO	详情	详情
(XI)	25003	7-methoxy-2-naphthol	5060-82-2	C₁₁H₁₀O₂	详情	详情
(XII)	25004	7-methoxy-2-naphthyl trifluoromethanesulfonate		C₁₂H₉F₃O₄S	详情	详情

Extended Information