propyl 3-methylbutanoate -Drug Synthesis Database

【结构式】

【分子编号】61621

【品名】propyl 3-methylbutanoate

【CA登记号】

【分子式】C₈H₁₆O₂

【分子量】144.21384

【元素组成】C 66.63% H 11.18% O 22.19%

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 condensation of benzaldehyde (I) with ethyl isovalerate (II) by means of hexyl lithium and DIA in THF gives the hydroxyester (III), which is acylated with Ac2O and DMAP in THF to yield the acetoxy derivative (IV). The elimination reaction in (IV) by means of t-BuOK in THF affords the unsaturated ester (V), which is reduced with diisobutylaluminum hydride in toluene to provide the unsaturated alcohol (VI). Finally, this compound is enantioselectively reduced with H2 over a chiral biphenylyl diphenylphosphine catalyst and a [Rh(norbornadiene)Cl]2 catalyst in toluene to give the target intermediate 2(R)-isopropyl-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-1-propanol (VII). (see scheme 26758001d, intermediate (XXIX)).

参考文献中间体

合成目标

【1】 Herold, P.; Stutz, S.; Spindler, F. (Speedel Pharma Inc.); Process for the preparation of (R)-2-alkyl-3-phenyl-1-propanols. WO 0202487 .

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)	61620	4-Methoxy-3-(3-methoxypropoxy)benzaldehyde	172900-75-3	C₁₂H₁₆O₄	详情	详情
(II)	61621	propyl 3-methylbutanoate		C₈H₁₆O₂	详情	详情
(III)	61622	propyl 2-{hydroxy[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-3-methylbutanoate		C₂₀H₃₂O₆	详情	详情
(IV)	61623	propyl 2-{(acetyloxy)[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-3-methylbutanoate		C₂₂H₃₄O₇	详情	详情
(V)	61624	propyl (E)-2-isopropyl-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-propenoate		C₂₀H₃₀O₅	详情	详情
(VI)	61625	(E)-2-isopropyl-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-propen-1-ol		C₁₇H₂₆O₄	详情	详情
(VII)	50573	(2R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methyl-1-butanol		C₁₇H₂₈O₄	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 condensation of benzaldehyde (I) with ethyl isovalerate (II) by means of hexyl lithium and DIA in THF gives the hydroxyester (III), which is acylated with Ac2O and DMAP in THF to yield the acetoxy derivate (IV). The elimination reaction in (IV) by means of t-BuOK in THF affords the unsaturated ester (V), which is hydrolyzed with KOH in ethanol to provide the unsaturated free acid (VI). Finally, this compound is enantioselectively reduced with H2 over several chiral Rh catalysts {[Rh(NBD)2BF4, [Rh(NBD)(OCOCF3)2], [Rh(NBD)Cl2], etc} to give the target intermediate 2(R)-isopropyl-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]propionic acid (VII). (see scheme 26758001a, intermediate (VII)).

参考文献中间体

合成目标

【1】 Herold, P.; Stutz, S. (Speedel Pharma Inc.); Preparation of (R)-2-alkyl-3-phenylpropionic acids. WO 0202500 .

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)	61620	4-Methoxy-3-(3-methoxypropoxy)benzaldehyde	172900-75-3	C₁₂H₁₆O₄	详情	详情
(II)	61621	propyl 3-methylbutanoate		C₈H₁₆O₂	详情	详情
(III)	61622	propyl 2-{hydroxy[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-3-methylbutanoate		C₂₀H₃₂O₆	详情	详情
(IV)	61623	propyl 2-{(acetyloxy)[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-3-methylbutanoate		C₂₂H₃₄O₇	详情	详情
(V)	61624	propyl (E)-2-isopropyl-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-propenoate		C₂₀H₃₀O₅	详情	详情
(VI)	61626	(E)-2-isopropyl-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-propenoic acid		C₁₇H₂₄O₅	详情	详情
(VII)	28119	(2R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyric acid		C₁₇H₂₆O₅	详情	详情

Extended Information