4,5-dimethoxy-7-methyl-1-naphthylboronic acid -Drug Synthesis Database

【结构式】

【分子编号】38316

【品名】4,5-dimethoxy-7-methyl-1-naphthylboronic acid

【CA登记号】

【分子式】C₁₃H₁₅BO₄

【分子量】246.0707

【元素组成】C 63.45% H 6.14% B 4.39% O 26.01%

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：(XIX)

The intermediate naphthaleneboronic acid (XIX) has been obtained as follows: The bromination of the 3-methylanisole (X) with NBS gives the dibromo compound (XI), which is treated with sodium phenylsulfinate to afford the sulfone (XII). The condensation of (XII) with methyl crotonate (XIII) by means of LDA and KOH gives the butyric acid (XIV), which is cyclized to the tetralone (XV) by means of trifluoroacetic anhydride (TFAA). The aromatization of (XV) by means of t-BuOK or NaOH yields the 5-bromo-8-methoxy-3-methyl-1-naphthol (XVI), which is methylated with dimethyl sulfate to afford the bis(methyl) ether (XVII). The reaction of (XVII) with trimethyl borate and n-BuLi gives the boronic ester (XVIII), which is hydrolyzed with water and ammonium chloride yielding the desired naphthaleneboronic acid (XIX). Alternatively, the naphthaleneboronic acid (XIX) has been obtained as follows: The reaction of 2,4-dibromoanisole (XX) with n-BuLi and cyclohexyl(isopropyl)amine gives the benzyne intermediate (XXI), which, without isolation is cyclized with the lithium enolate of 3-methylcrotonic acid dimethylamide (XXII) to afford the previously described naphthol (XVI), which is purified by chromatography.

参考文献中间体

合成目标

【1】 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	38309	1-methoxy-3-methylbenzene; methyl 3-methylphenyl ether	100-84-5	C₈H₁₀O	详情	详情
(XI)	27552	1-bromo-2-(bromomethyl)-4-methoxybenzene		C₈H₈Br₂O	详情	详情
(XII)	38310	(2-bromo-5-methoxybenzyl)(dioxo)phenyl-lambda(6)-sulfane; 2-bromo-5-methoxybenzyl phenyl sulfone		C₁₄H₁₃BrO₃S	详情	详情
(XIII)	26361	methyl (E)-2-butenoate	623-43-8	C₅H₈O₂	详情	详情
(XIV)	38311	4-(2-bromo-5-methoxyphenyl)-3-methyl-4-(phenylsulfonyl)butyric acid		C₁₈H₁₉BrO₅S	详情	详情
(XV)	38312	5-bromo-8-methoxy-3-methyl-4-(phenylsulfonyl)-3,4-dihydro-1(2H)-naphthalenone		C₁₈H₁₇BrO₄S	详情	详情
(XVI)	38313	5-bromo-8-methoxy-3-methyl-1-naphthol		C₁₂H₁₁BrO₂	详情	详情
(XVII)	38314	5-bromo-1,8-dimethoxy-3-methylnaphthalene; 4-bromo-8-methoxy-6-methyl-1-naphthyl methyl ether		C₁₃H₁₃BrO₂	详情	详情
(XVIII)	38315	dimethyl 4,5-dimethoxy-7-methyl-1-naphthylboronate		C₁₅H₁₉BO₄	详情	详情
(XIX)	38316	4,5-dimethoxy-7-methyl-1-naphthylboronic acid		C₁₃H₁₅BO₄	详情	详情
(XX)	38317	2,4-dibromophenyl methyl ether; 2,4-dibromo-1-methoxybenzene	21702-84-1	C₇H₆Br₂O	详情	详情
(XXI)	38318	4-bromo-1,3-cyclohexadien-5-yn-1-yl methyl ether; 1-bromo-4-methoxy-1,3-cyclohexadien-5-yne		C₇H₅BrO	详情	详情
(XXII)	37859			C₈H₁₄LiNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIX)

The condensation of the isoquinoline intermediate (IX) with the naphthaleneboronic acid intermediate (XIX) by means of palladium tetrakis(triphenylphosphine) and NaHCO3 in refluxing ethanol/toluene gives a 5:4 mixture of the (S) and (R) atropaisomers (XXIII), which, without separation, is submitted to debenzylation by means of H2 over Pd/C in methanol/dichloromethane affording a mixture of the target (S-biar) compound, along with its (R-biar)-atropaisomer that are separated by HPLC.

参考文献中间体

合成目标

【1】 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(S)-(XXIII)	38319	(1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-(4,5-dimethoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline; benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-(4,5-dimethoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether	C₄₆H₄₇NO₅	详情	详情
(S-biar)	38320	(1R,3R)-5-(4,5-dimethoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol	C₂₄H₂₇NO₄	详情	详情
(R)-(XXIII)	63435	2-benzyl-6,8-bis(benzyloxy)-5-[5-methoxy-4-(methoxymethoxy)-7-methyl-1-naphthyl]-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline; benzyl 2-benzyl-6-(benzyloxy)-5-[5-methoxy-4-(methoxymethoxy)-7-methyl-1-naphthyl]-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether	C₄₆H₄₇NO₅	详情	详情
(IX)	37847	benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline	C₃₂H₃₂INO₂	详情	详情
(XIX)	38316	4,5-dimethoxy-7-methyl-1-naphthylboronic acid	C₁₃H₁₅BO₄	详情	详情

Extended Information