2-(tributylstannyl)-2,3-pentadienyl pivalate -Drug Synthesis Database

【结构式】

【分子编号】11569

【品名】2-(tributylstannyl)-2,3-pentadienyl pivalate

【CA登记号】

【分子式】C₂₂H₄₂O₂Sn

【分子量】457.28428

【元素组成】C 57.79% H 9.26% O 7% Sn 25.96%

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：(II)

The synthesis of the C22-C34 subunit (C12-C16 of the chemical name) of FK-506 has been reported: The condensation of the chiral aldehyde (I) with the (S)-allenyl stannane (II) by means of boron trifluoride ethearate in dichloromethane yields an epimeric mixture of the acetylenic alcohol (III), which by protection with p-methoxybenzyl (PMB) trichloroacetimidate, followed by chromatographic separation, gives the enantiomerically pure protected acetylenic diol (IV). The reduction of (IV) with bis(2-methoxyethoxy)aluminum hydride in THF affords the (E,E)-dienic alcohol (V), which is submitted to a Sharpless asymmetric epoxidation with (-)-diethyl tartrate [(-)-DETR], titanium tetraisopropoxide and tert-butyl hydroperoxide (TBHP) in dichloromethane, yielding the chiral epoxy alcohol (VI). The reduction of (VI) with bis(2-methoxyethoxy)aluminum hydride in THF affords the partially protected triol (VII), which is finally dehydrogenated with dichlorodicyanobenzoquinone (DDQ) in dichloromethane to give the chiral 1,3-dioxane (VIII), which is the desired intermediate.

参考文献中间体

合成目标

【1】 Marshall, J.A.; Xie, S.P.; Synthesis of a C22-34 subunit of the immunosuppressant FK-506. J Org Chem 1995, 60, 22, 7230.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	63307	1,1,1-trichloro-3-(4-methoxyphenyl)-2-propanimine	C₁₀H₁₀Cl₃NO	详情	详情
(I)	11534	(E)-3-[(1R,3R,4R)-3-Methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-2-methyl-2-propenal	C₂₀H₃₈O₃Si	详情	详情
(II)	11569	2-(tributylstannyl)-2,3-pentadienyl pivalate	C₂₂H₄₂O₂Sn	详情	详情
(III)	11570	(4R,6E)-5-hydroxy-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-hepten-2-ynyl pivalate	C₃₀H₅₄O₅Si	详情	详情
(IV)	11571	(4R,5S,6E)-5-[(4-methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-hepten-2-ynyl pivalate	C₃₈H₆₂O₆Si	详情	详情
(V)	11572	(2E,4R,5S,6E)-5-[(4-Methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-2,6-heptadien-1-ol	C₃₃H₅₆O₅Si	详情	详情
(VI)	11573	[(2R,3R)-3-((1S,2S,3E)-2-[(4-Methoxybenzyl)oxy]-4-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1,3-dimethyl-3-butenyl)oxiranyl]methanol	C₃₃H₅₆O₆Si	详情	详情
(VII)	11574	(3S,4R,5S,6E)-5-[(4-Methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-heptene-1,3-diol	C₃₃H₅₈O₆Si	详情	详情
(VIII)	11575	2-[(4S,5S,6S)-2-(4-Methoxyphenyl)-6-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-5-methyl-1,3-dioxan-4-yl]-1-ethanol	C₃₃H₅₆O₆Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The starting compounds (I) and (II) are obtained as follows: Aldehyde (I): The esterification of (R,R)-dihydrobenzoin (IX) with acryloyl chloride (X) by means of triethylamine in dichloromethane gives the corresponding diester (XI), which by bis-cyclization with butadiene (XII) by means of TiCl4 in dichloromethane yields the bis(3-cyclohexenecarboxylic acid) ester (XIII). The hydrolysis of (XIII) with LiOH in methanol affords (R)-3-cyclohexenecarboxylic acid (XIV), which by reaction with I2, KI and NaHCO3 is converted to the iodolactone (XV). The reaction of (XV) with 1,5-diazabicyclo[5.4.0]-5-undecene (DBU) in refluxing THF affords the unsaturated lactone (XVI), which by treatment with NaHCO3 in anhydrous methanol yields (1R,3R)-3-hydroxy-4-cyclohexenecarboxylic acid methyl ester (XVII). The methylation of (XVII) with methyl trifluoromethanesulfonate and 2,6-di-tert-butyl-4-methylpyridine (DBMP) in dichloromethane gives the 3-methoxy ester (XVIII), which is selectively hydroxylated with BH3, H2O2 and NaOH to (1R,3R,4R)-4-hydroxy-3-methoxycyclohexanecarboxylic acid methyl ester (XIX). The protection of (XIX) with triisopropylsilyl (TIPS) trifluoromethanesulfonate (XX) and triethylamine in dichloromethane affords the protected ester (XXI), which is reduced with dibutylaluminum hydride (DIBAL) in hexane to the corresponding aldehyde (XXII). Finally, this compound is condensed with the N-tert-butylimine of 2-(triethylsilyl)propanol (XXIII) by means of butyllithium in THF to afford the desired aldehyde (I) (Scheme 2). Allenyl stannane (II): The silylation of (R)-methyl lactate (XXIV) with tert-butyldimethylsilyl chloride (TBS-Cl) and imidazole in DMF gives the silyl ether (XXV), which is reduced with DIBAL to the corresponding aldehyde (XXVI). The reaction of (XXVI) with tetrabromomethane and triphenylphosphine in dichloromethane affords 3(R)-(tert-butyldimethysilyloxy)-1,1-dibromo-1-butene (XXVII), which by reaction with butyllithium and formaldehyde is converted to the corresponding 2-pentyn-1-ol (XXVIII). The esterification of (XXVIII) with pivaloyl (PIV) chloride and NaHCO3 in dichloromethane yields the pivaloyl ester (XXIX), which is desilylated with tetrabutylammonium fluoride (TBAF) in THF, giving the hydroxy ester (XXX). The mesylation of (XXX) with methanesulfonyl chloride and triethylamine in dichloromethane affords the sulfonate (XXXI), which is finally treated with the lithium derivative of tributylstannyl hydride, CuBr and dimethylsulfide in THF to afford the desired allenyl stannane (II).

参考文献中间体

合成目标

【1】 Marshall, J.A.; Xie, S.P.; Synthesis of a C22-34 subunit of the immunosuppressant FK-506. J Org Chem 1995, 60, 22, 7230.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	11569	2-(tributylstannyl)-2,3-pentadienyl pivalate		C₂₂H₄₂O₂Sn	详情	详情
(XXIV)	11591	methyl (2R)-2-hydroxypropanoate	17392-83-5	C₄H₈O₃	详情	详情
(XXV)	11592	methyl (2R)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoate		C₁₀H₂₂O₃Si	详情	详情
(XXVI)	11593	(2R)-2-[[tert-Butyl(dimethyl)silyl]oxy]propanal		C₉H₂₀O₂Si	详情	详情
(XXVII)	11594	tert-Butyl(dimethyl)silyl (1R)-3,3-dibromo-1-methyl-2-propenyl ether; tert-Butyl[[(1R)-3,3-dibromo-1-methyl-2-propenyl]oxy]dimethylsilane		C₁₀H₂₀Br₂OSi	详情	详情
(XXVIII)	11595	(4R)-4-[[tert-Butyl(dimethyl)silyl]oxy]-2-pentyn-1-ol		C₁₁H₂₂O₂Si	详情	详情
(XXIX)	11596	(4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-pentynyl pivalate		C₁₆H₃₀O₃Si	详情	详情
(XXX)	11597	(4R)-4-hydroxy-2-pentynyl pivalate		C₁₀H₁₆O₃	详情	详情
(XXXI)	11598	(4R)-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-pentynyl pivalate		C₁₃H₂₂O₃S	详情	详情

Extended Information