(1S)-1-methyl-2-oxobutyl benzoate -Drug Synthesis Database

【结构式】

【分子编号】42623

【品名】(1S)-1-methyl-2-oxobutyl benzoate

【CA登记号】

【分子式】C₁₂H₁₄O₃

【分子量】206.24136

【元素组成】C 69.89% H 6.84% O 23.27%

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：(XII)

The intermediate (XXI) has been obtained as follows: The condensation of the chiral benzylated hydroxypentanone (XII) with the chiral aldehyde (XIII) by means of DCHBCl gives the chiral hydroxyheptanone (XIV), which is protected at the OH group with p-methoxybenzyl trichloroacetimidate (Pmb-Tca), yielding the expected benzyl ether (XV). The reduction of the CO group of (XV) by means of LiAlH4, with simultaneous debenzylation affords the alpha-diol (XVI), which is oxidized with NaIO4 to provide the aldehyde (XVII). The condensation of (XVII) with the allyl compound (XVIII) by means of CrCl2 and KH in THF gives the octadiene compound (XIX), which is desilylated with camphorsulfonic acid (CSA) to yield the unsaturated alcohol (XX). Finally, this alcohol is oxidized with DMP to the desired intermediate aldehyde (XXI).

参考文献中间体

合成目标

【1】 Paterson, I.; Florence, G.J.; Synthesis of (+)-discodermolide and analogues by control of asymmetric induction in aldol reactions of gamma-chiral (Z)-enals. Tetrahedron Lett 2000, 41, 35, 6935.
【2】 Paterson, I.; et al.; Total synthesis of the antimicrotubule agent (+)-discodermolide using boron-mediated aldol reactions of chiral ketones. Angew Chem. Int Ed Engl 2000, 39, 2, 377.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	42623	(1S)-1-methyl-2-oxobutyl benzoate		C₁₂H₁₄O₃	详情	详情
(XIII)	42624	(2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropanal		C₁₀H₂₂O₂Si	详情	详情
(XIV)	42625	(1S,3R,4R,5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-hydroxy-1,3,5-trimethyl-2-oxohexyl benzoate		C₂₂H₃₆O₅Si	详情	详情
(XV)	42626	(1S,3R,4R,5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-1,3,5-trimethyl-2-oxohexyl benzoate		C₃₀H₄₄O₆Si	详情	详情
(XVI)	42627	(2S,4S,5R,6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-5-[(4-methoxybenzyl)oxy]-4,6-dimethyl-2,3-heptanediol		C₂₃H₄₂O₅Si	详情	详情
(XVII)	42628	(2R,3R,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal		C₂₁H₃₆O₄Si	详情	详情
(XVIII)	42629	(1-bromo-2-propenyl)(trimethyl)silane	94397-40-7	C₆H₁₃BrSi	详情	详情
(XIX)	42630	tert-butyl([(2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienyl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienyl ether		C₂₄H₄₀O₃Si	详情	详情
(XX)	42631	(2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadien-1-ol		C₁₈H₂₆O₃	详情	详情
(XXI)	42632	(2R,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienal		C₁₈H₂₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

Chiral pentanoic aldehyde intermediate (XIX): The reaction of the chiral benzoate ester (XII) with (c-Hex)2B-Cl and Me2EtN in ethyl ether gives the boron enolate (XIII), which is condensed with the propionaldehyde (XIV) to yield the benzoate ester (XV). The protection of the OH group of (XV) by means of p-methoxybenzyl trichloroacetimidate and Tf-OH affords the corresponding p-methoxybenzyl ether (XVI). The reduction of the ketonic group of (XVI) by means of LiAlH4 in THF or NaBH4 in methanol provides the alcohol (XVII), which is debenzoylated with K2CO3 in methanol to furnish the diol (XVIII). Finally the vicinal diol (XVIII) is oxidized with NaIO4 in aqueous methanol to obtain the target, chiral pentanoic aldehyde intermediate (XIX).

参考文献中间体

合成目标

【1】 Paterson, I.; Florence, G.J.; Gerlach, K.; Scott, J.P.; Sereinig, N.; A practical synthesis of (+)-discodermolide and analogues: Fragment union by complex aldol reactions. J Am Chem Soc 2001, 123, 39, 9535.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XII)	42623	(1S)-1-methyl-2-oxobutyl benzoate	C₁₂H₁₄O₃	详情	详情
(XIII)	62838	(1S,2E)-2-{[cyclohexyl(methyl)boryl]oxy}-1-methyl-2-butenyl benzoate	C₁₉H₂₇BO₃	详情	详情
(XIV)	42624	(2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropanal	C₁₀H₂₂O₂Si	详情	详情
(XV)	42625	(1S,3R,4R,5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-hydroxy-1,3,5-trimethyl-2-oxohexyl benzoate	C₂₂H₃₆O₅Si	详情	详情
(XVI)	42626	(1S,3R,4R,5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-1,3,5-trimethyl-2-oxohexyl benzoate	C₃₀H₄₄O₆Si	详情	详情
(XVII)	62839	(1S,3S,4R,5S)-6-{[tert-butyl(dimethyl)silyl]oxy}-2-hydroxy-4-[(4-methoxybenzyl)oxy]-1,3,5-trimethylhexyl benzoate	C₃₀H₄₆O₆Si	详情	详情
(XVIII)	42627	(2S,4S,5R,6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-5-[(4-methoxybenzyl)oxy]-4,6-dimethyl-2,3-heptanediol	C₂₃H₄₂O₅Si	详情	详情
(XIX)	42628	(2R,3R,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal	C₂₁H₃₆O₄Si	详情	详情

Extended Information