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【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

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).

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).

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 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) 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