[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanol -Drug Synthesis Database

【结构式】

【分子编号】18084

【品名】[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanol

【CA登记号】

【分子式】C₂₁H₂₆O₃

【分子量】326.43564

【元素组成】C 77.27% H 8.03% O 14.7%

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：(XXV)

The esterification of (rac)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid (XXII) with diazomethane gives the methyl ester (XXIII), which is treated with Bn-Br and K2CO3 yielding the benzyl ether (XXIV). The reduction of the ester group of (XXIV) with LiAlH4 provides the carbinol (XXV), which is debenzylated with H2 over Pd/C to afford the racemic phenol (rac)-(XXVI). Optical resolution of (XXVI) by means of lipase PL-266 and vinyl acetate gives the chiral acetate (S)-(XXVII), which is rebenzylated with BnBr yielding the benzyl ether (XXVIII). The deacetylation of (XXVIII) with LiAlH4 in ethyl ether affords the carbinol (XXIX), which is oxidized with oxalyl chloride to the aldehyde (XXX). The condensation of (XXX) with the intermediate phosphonium salt (XXI) by means of n-BuLi in THF gives the olefin (XXXI), which is finally hydrogenated and debenzylated with H2 over Pd/C in ethyl acetate.

参考文献中间体

合成目标

【1】 Nozawa, M.; et al.; Enantioselective synthesis of (2R,4'R,8'R)-alpha-tocopherol (vitamin E) based on enzymatic function. Chem Pharm Bull 2000, 48, 2, 272.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXI)	40910	triphenyl[(3R,7R)-3,7,11-trimethyldodecyl]phosphonium bromide		C₃₃H₄₆BrP	详情	详情
(XXII)	21255	Trolox; Trolox C; 6-hydroxy-2,5,7,8-tetramethyl-2-chromanecarboxylic acid	53188-07-1	C₁₄H₁₈O₄	详情	详情
(XXIII)	40911	methyl 6-hydroxy-2,5,7,8-tetramethyl-2-chromanecarboxylate		C₁₅H₂₀O₄	详情	详情
(XXIV)	40912	methyl 6-(benzyloxy)-2,5,7,8-tetramethyl-2-chromanecarboxylate		C₂₂H₂₆O₄	详情	详情
(XXV)	18084	[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanol		C₂₁H₂₆O₃	详情	详情
(XXVI)	21256	2-(hydroxymethyl)-2,5,7,8-tetramethyl-6-chromanol		C₁₄H₂₀O₃	详情	详情
(XXVII)	40913	[(2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl acetate		C₁₆H₂₂O₄	详情	详情
(XXVIII)	40914	[(2S)-6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl acetate		C₂₃H₂₈O₄	详情	详情
(XXIX)	40915	[(2S)-6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanol		C₂₁H₂₆O₃	详情	详情
(XXX)	40916	(2S)-6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-carbaldehyde		C₂₁H₂₄O₃	详情	详情
(XXXI)	40917	(2S)-6-(benzyloxy)-2,5,7,8-tetramethyl-2-[(E,4R,8R)-4,8,12-trimethyl-1-tridecenyl]-3,4-dihydro-2H-chromene; benzyl (2S)-2,5,7,8-tetramethyl-2-[(E,4R,8R)-4,8,12-trimethyl-1-tridecenyl]-3,4-dihydro-2H-chromen-6-yl ether		C₃₆H₅₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Treatment of chromane (I) with metanesulfonyl chloride in pyridine at 0 C afforded mesylate (II), which was treated with 2-methylaminoethanol (III) to afford tertiary amine (IV). Reaction with SOCl2 gave chloride (V), and further reaction with p-hydroxybenzaldehyde (VI) provided (VII). Aldehyde (VII) was then condensed with 2,4-thiazolidinedione (VIII) in the presence of piperidine benzoate in toluene to furnish (IX). Finally, the benzyl protecting group was removed by treatment with acetic acid-hydrochloric acid at 60 C to give the title compound.

参考文献中间体

合成目标

【1】 Reddy, K.A.; Lohray, B.B.; Bhushan, V.; Reddy, A.S.; Kishore, P.H.; Rao, VV.; Saibaba, V.; Bajji, A.C.; Rajesh, B.M.; Reddy, K.V.; Chakrabarti, R.; Rajagopalan, R.; Novel euglycemic and hypolipidemic agents: Part-2. Antioxidant moiety as structural motif. Bioorg Med Chem Lett 1998, 8, 9, 999-1002.

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)	18084	[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanol		C₂₁H₂₆O₃	详情	详情
(II)	18085	[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl methanesulfonate		C₂₂H₂₈O₅S	详情	详情
(III)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情
(IV)	18086	2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]-1-ethanol		C₂₄H₃₃NO₃	详情	详情
(V)	18087	N-[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl]-N-(2-chloroethyl)-N-methylamine; N-[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl]-2-chloro-N-methyl-1-ethanamine		C₂₄H₃₂ClNO₂	详情	详情
(VI)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(VII)	18088	4-[2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]ethoxy]benzaldehyde		C₃₁H₃₇NO₄	详情	详情
(VIII)	10883	1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione	2295-31-0	C₃H₃NO₂S	详情	详情
(IX)	18089	5-[(Z)-(4-[2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]ethoxy]phenyl)methylidene]-1,3-thiazolidine-2,4-dione		C₃₄H₃₈N₂O₅S	详情	详情

Extended Information