(6R,7S)-5,6,7,8-tetrahydro-1,6,7-naphthalenetriol -Drug Synthesis Database

【结构式】

【分子编号】40442

【品名】(6R,7S)-5,6,7,8-tetrahydro-1,6,7-naphthalenetriol

【CA登记号】

【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：(III)

The esterification of 5,8-dihydro-1-naphthol (I) with acetic anhydride gives the corresponding acetate (II), which is oxidized with silver acetate and I2 in acetic acid to yield 2,3-cis-1,2,3,4-tetrahydro-2,3,5-naphthalenetriol (III). The treatment of this product with sodium methylate and epichlorhydrin (A) in methanol gives 2,3-cis-1,2,3,4-tetrahydro-5-(2,3-epoxypropoxy)-2,3-naphthalenediol (IV), which is finally treated with tertbutylamine (B) in chloroform-methanol.

参考文献中间体

合成目标

【1】 Hanck, F.P.; et al.; Tetrahydronaphthyloxyaminopropanols and related compounds. CA 979926; DE 2258995; GB 1358722 .
【2】 Weetman, D.F.; Castaner, J.; Nadolol. Drugs Fut 1976, 1, 9, 434.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(B)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情
(I)	40440	5,8-dihydro-1-naphthalenol	27673-48-9	C₁₀H₁₀O	详情	详情
(II)	40441	1-naphthyl acetate	830-81-9	C₁₂H₁₀O₂	详情	详情
(III)	40442	(6R,7S)-5,6,7,8-tetrahydro-1,6,7-naphthalenetriol		C₁₀H₁₂O₃	详情	详情
(IV)	40443	(2R,3S)-5-(2-oxiranylmethoxy)-1,2,3,4-tetrahydro-2,3-naphthalenediol		C₁₃H₁₆O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

In a different procedure, the previously reported acetal (XI) was hydrolyzed under acidic conditions to give triol (XII). Oxidative cleavage of the cyclic diol function of (XII) by means of NaIO4 gave rise to the dialdehyde (XIII), which was further subjected to a reductive treatment with NaBH4, yielding triol (XIV). Tosylation of the aliphatic hydroxyl groups of (XIV) produced the ditosylate (XV) which, upon treatment with K2CO3 in MeOH, underwent intramolecular cyclization to the dihydrobenzofuran (XVI). Elimination of the remaining tosylate group of (XVI) in the presence of potassium tert-butoxide afforded the styrene derivative (XVII). Subsequent cycloaddition between styrene (XVII) and the enol triflate generated from N,N-dimethylisobutyramide (XVIII) produced the cyclobutanone (XIX). Halogenation of the lithium enolate of ketone (XIX) with N-bromosuccinimide in cold THF yielded the bromo ketone (XX). This underwent a Favorskii rearrangement in the presence of NaOH, producing the corresponding racemic cyclopropanecarboxylic acid, which was resolved by formation of the diastereomeric salts with (+)-alpha-methylbenzylamine. The desired (R,R)-acid (IX) was finally coupled with guanidine (X) via activation with CDI as above.

参考文献中间体

合成目标

【1】 Wu, S.C.; Atwal, K.S.; Dugar, S.; Ahmad, S. (Bristol-Myers Squibb Co.); Acyl guanidine sodium/proton exchange inhibitors and method. EP 1041980; JP 2001527042; US 6011059; WO 9933460 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	51883	(1R,3R)-3-(2,3-dihydro-1-benzofuran-4-yl)-2,2-dimethylcyclopropanecarboxylic acid		C₁₄H₁₆O₃	详情	详情
(X)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(XI)	51884	(3aS,9aR)-2,2-dimethyl-3a,4,9,9a-tetrahydronaphtho[2,3-d][1,3]dioxol-5-ol		C₁₃H₁₆O₃	详情	详情
(XII)	40442	(6R,7S)-5,6,7,8-tetrahydro-1,6,7-naphthalenetriol		C₁₀H₁₂O₃	详情	详情
(XIII)	51885	2-[2-hydroxy-6-(2-oxoethyl)phenyl]acetaldehyde		C₁₀H₁₀O₃	详情	详情
(XIV)	51886	2,3-bis(2-hydroxyethyl)phenol		C₁₀H₁₄O₃	详情	详情
(XV)	51887	3-hydroxy-2-(2-[[(4-methylphenyl)sulfonyl]oxy]ethyl)phenethyl 4-methylbenzenesulfonate		C₂₄H₂₆O₇S₂	详情	详情
(XVI)	51888	2-(2,3-dihydro-1-benzofuran-4-yl)ethyl 4-methylbenzenesulfonate		C₁₇H₁₈O₄S	详情	详情
(XVII)	51889	4-vinyl-2,3-dihydro-1-benzofuran		C₁₀H₁₀O	详情	详情
(XVIII)	51890	N,N,2-Trimethylpropionamide; N,N-Dimethylisobutyramide	21678-37-5	C₆H₁₃NO	详情	详情
(XIX)	51891	3-(2,3-dihydro-1-benzofuran-4-yl)-2,2-dimethylcyclobutanone		C₁₄H₁₆O₂	详情	详情
(XX)	51892	4-bromo-3-(2,3-dihydro-1-benzofuran-4-yl)-2,2-dimethylcyclobutanone		C₁₄H₁₅BrO₂	详情	详情

Extended Information