2-bromo-4-isopropoxybenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】35400

【品名】2-bromo-4-isopropoxybenzoic acid

【CA登记号】

【分子式】C₁₀H₁₁BrO₃

【分子量】259.09954

【元素组成】C 46.36% H 4.28% Br 30.84% O 18.53%

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：(I)

2-Bromo-5-isopropoxybenzoic acid (I) was treated with oxalyl chloride to give the corresponding acid chloride (II) and subsequently condensed with the enantiomerically pure tetrahydroisoquinoline (III), yielding ester (IV). Intramolecular biaryl coupling by means of palladium acetate and tri(o-tolylphosphine) produced lactone (V), existing as an interconvertible mixture of its two atropo-diastereomeric forms. Reductive ring cleavage of this lactone using several hydride transfer reagents gave a separable mixture of two atropisomeric diols, from which the S-biar atropisomer (VI) was isolated by chromatography. After protection of the phenolic hydroxyl group of (VI) as the isopropyl ether (VII), oxidation of the primary alcohol with pyridinium chlorochromate (PCC) gave aldehyde (VIII). Stobbe condensation of (VIII) with diethyl succinate (IX) and NaOEt afforded the benzylidene succinic derivative (X).

参考文献中间体

合成目标

【1】 Bringmann, G.; et al.; First atropo-divergent total synthesis of the antimalarial korupensamines A and B by the "lactone method". J Org Chem 2000, 65, 7, 2069.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	32658	2-bromopropane	75-26-3	C₃H₇Br	详情	详情
(I)	35400	2-bromo-4-isopropoxybenzoic acid		C₁₀H₁₁BrO₃	详情	详情
(II)	35401	2-bromo-4-isopropoxybenzoyl chloride		C₁₀H₁₀BrClO₂	详情	详情
(III)	35402	(1R,3R)-2-benzyl-8-isopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-6-isoquinolinol		C₂₁H₂₇NO₂	详情	详情
(IV)	35403	(1R,3R)-2-benzyl-8-isopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-6-isoquinolinyl 2-bromo-4-isopropoxybenzoate		C₃₁H₃₆BrNO₄	详情	详情
(V)	35404	(2R,4R)-3-benzyl-5,10-diisopropoxy-2,4-dimethyl-1,2,3,4-tetrahydro-8H-isochromeno[4,3-f]isoquinolin-8-one		C₃₁H₃₅NO₄	详情	详情
(VI)	35405	(1R,3R)-2-benzyl-5-[2-(hydroxymethyl)-4-isopropoxyphenyl]-8-isopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-6-isoquinolinol		C₃₁H₃₉NO₄	详情	详情
(VII)	35406	[2-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxyphenyl]methanol		C₃₄H₄₅NO₄	详情	详情
(VIII)	35407	2-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxybenzaldehyde		C₃₄H₄₃NO₄	详情	详情
(IX)	12313	diethyl succinate	123-25-1	C₈H₁₄O₄	详情	详情
(X)	35408	(E)-4-[2-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxyphenyl]-3-(ethoxycarbonyl)-3-butenoic acid		C₄₀H₅₁NO₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

2-Bromo-5-isopropoxybenzoic acid (I) was treated with oxalyl chloride to give the corresponding acid chloride (II) and subsequently condensed with the enantiomerically pure tetrahydroisoquinoline (III), yielding ester (IV). Intramolecular biaryl coupling by means of palladium acetate and tri(o-tolylphosphine) produced lactone (V), existing as an interconvertible mixture of its two atropo-diastereomeric forms. Reductive ring cleavage of this lactone using several hydride transfer reagents gave a separable mixture of two atropisomeric diols, from which the R-biar atropisomer (VI) was isolated by chromatography. After protection of the phenolic hydroxyl group of (VI) as the isopropyl ether (VII), oxidation of the primary alcohol with pyridinium chlorochromate (PCC) gave aldehyde (VIII). Stobbe condensation of (VIII) with diethyl succinate (IX) and NaOEt afforded the benzylidene succinic derivative (X).

参考文献中间体

合成目标

【1】 Bringmann, G.; et al.; First atropo-divergent total synthesis of the antimalarial korupensamines A and B by the "lactone method". J Org Chem 2000, 65, 7, 2069.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	32658	2-bromopropane	75-26-3	C₃H₇Br	详情	详情
(I)	35400	2-bromo-4-isopropoxybenzoic acid		C₁₀H₁₁BrO₃	详情	详情
(II)	35401	2-bromo-4-isopropoxybenzoyl chloride		C₁₀H₁₀BrClO₂	详情	详情
(III)	35402	(1R,3R)-2-benzyl-8-isopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-6-isoquinolinol		C₂₁H₂₇NO₂	详情	详情
(IV)	35403	(1R,3R)-2-benzyl-8-isopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-6-isoquinolinyl 2-bromo-4-isopropoxybenzoate		C₃₁H₃₆BrNO₄	详情	详情
(V)	35404	(2R,4R)-3-benzyl-5,10-diisopropoxy-2,4-dimethyl-1,2,3,4-tetrahydro-8H-isochromeno[4,3-f]isoquinolin-8-one		C₃₁H₃₅NO₄	详情	详情
(VI)	35405	(1R,3R)-2-benzyl-5-[2-(hydroxymethyl)-4-isopropoxyphenyl]-8-isopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-6-isoquinolinol		C₃₁H₃₉NO₄	详情	详情
(VII)	35406	[2-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxyphenyl]methanol		C₃₄H₄₅NO₄	详情	详情
(VIII)	35407	2-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxybenzaldehyde		C₃₄H₄₃NO₄	详情	详情
(IX)	12313	diethyl succinate	123-25-1	C₈H₁₄O₄	详情	详情
(X)	35408	(E)-4-[2-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxyphenyl]-3-(ethoxycarbonyl)-3-butenoic acid		C₄₀H₅₁NO₇	详情	详情

Extended Information