2-[(1R,2R,3S,6S,7S)-5-oxo-4,10-dioxatricyclo[5.2.1.0(2,6)]dec-3-yl]benzaldehyde -Drug Synthesis Database

【结构式】

【分子编号】36478

【品名】2-[(1R,2R,3S,6S,7S)-5-oxo-4,10-dioxatricyclo[5.2.1.0(2,6)]dec-3-yl]benzaldehyde

【CA登记号】

【分子式】C₁₅H₁₄O₄

【分子量】258.27376

【元素组成】C 69.76% H 5.46% O 24.78%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XVI)

The synthesis of [1S-(1alpha,2alpha,3alpha,4alpha)]-2-[2-[2-(methoxycarbonyl)ethyl]benzyl]-7-oxabicyclo[2.2.1]heptane-3-carboxylic acid (VI), a key intermediate in the synthesis of 203961 [see scheme 20396101a] has been presented: This compound has been obtained by two similar ways: 1) The condensation of L-valinol (XII) with anhydride (XXII) catalyzed by oxalic acid gives imide (XIII), which is treated with ethylmagnesium chloride, the Grignard reagent (XIV) and NaBH4 yielding intermediate (XV). This intermediate, without isolation, is treated with HCl in THF to afford the substituted benzaldehyde (XVI), which is condensed with trimethyl phosphonoacetate (XVII) and DBU in acetonitrile giving the propenoic ester (XVIII). Finally, this compound is submitted to a simultaneous reduction and hydrogenolysis with H2 over a Pearlman catalyst in methanol to provide the target of [1S-(1alpha,2alpha,3alpha,4alpha)]-2-[2-[2-(methoxycarbonyl)ethyl]benzyl]-7-oxabicyclo[2.2.1]heptane-3-carboxylic acid (VI). 2) The preceding reaction sequence can also be performed using (S)-2-phenylglycinol (XIX) instead of the L-valinol (XII) yielding the previously reported benzaldehyde (XVI) through the imide (XX) and the nonisolated intermediate (XXI).

参考文献中间体

合成目标

【1】 Mueller, R.H.; et al.; Diastereoselective reaction of a grignard reagent with chiral imides: A practical preparation of a key intermediate in the synthesis of ifetroban sodium. Org Process Res Dev 1997, 1, 1, 14.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	14870	(1R,2S,3R,4S)-3-[2-(3-methoxy-3-oxopropyl)benzyl]-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid		C₁₈H₂₂O₅	详情	详情
(XII)	36480	(2S)-2-amino-3-methyl-1-butanol; (S)-(+)-Valinol; L-Valinol	2026-48-4	C₅H₁₃NO	详情	详情
(XIII)	36473	(1R,2R,6S,7S)-4-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-10-oxa-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₁₃H₁₉NO₄	详情	详情
(XIV)	36475	bromo[2-(1,3-dioxolan-2-yl)phenyl]magnesium		C₉H₉BrMgO₂	详情	详情
(XV)	36476	(1S,2S,5R,6R,7R)-4-[(1S)-1,2-dimethylpropyl]-5-[2-(1,3-dioxolan-2-yl)phenyl]-5-hydroxy-10-oxa-4-azatricyclo[5.2.1.0(2,6)]decan-3-one		C₂₂H₂₉NO₅	详情	详情
(XVI)	36478	2-[(1R,2R,3S,6S,7S)-5-oxo-4,10-dioxatricyclo[5.2.1.0(2,6)]dec-3-yl]benzaldehyde		C₁₅H₁₄O₄	详情	详情
(XVII)	13272	Methyl 2-(dimethoxyphosphoryl)acetate; Trimethyl phosphoroacetate	5927-18-4	C₅H₁₁O₅P	详情	详情
(XVIII)	36479	methyl (E)-3-[2-[(1R,2R,3S,6S,7S)-5-oxo-4,10-dioxatricyclo[5.2.1.0(2,6)]dec-3-yl]phenyl]-2-propenoate		C₁₈H₁₈O₅	详情	详情
(XIX)	10973	(2S)-2-Amino-2-phenyl-1-ethanol; (S)-2-Hydroxy-1-phenylethylamine; (S)-(+)-2-Phenylglycinol; (S)-2-Amino-2-phenyl-1-ethanol	20989-17-7	C₈H₁₁NO	详情	详情
(XX)	36474	(1R,2R,6S,7S)-4-[(1R)-2-hydroxy-1-phenylethyl]-10-oxa-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₁₆H₁₇NO₄	详情	详情
(XXI)	36477	(1S,2S,5R,6R,7R)-5-[2-(1,3-dioxolan-2-yl)phenyl]-5-hydroxy-4-[(1S)-1-phenylethyl]-10-oxa-4-azatricyclo[5.2.1.0(2,6)]decan-3-one		C₂₅H₂₇NO₅	详情	详情
(XXII)	36472	(1R,2R,6S,7S)-4,10-dioxatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₈H₈O₄	详情	详情

Extended Information