2-(Benzylanilino)-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】12655

【品名】2-(Benzylanilino)-1-ethanol

【CA登记号】

【分子式】C₁₅H₁₇NO

【分子量】227.30612

【元素组成】C 79.26% H 7.54% N 6.16% O 7.04%

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：(VII)

A new synthesis for (4S)-efonidipine has been described: The reaction of 5,5-dimethyl-2-(2-oxopropyl)-1,3,2-dioxaphosphorinan-2-one (I) with dimorpholino(3-nitrophenyl)methane (II) by means of trifluoroacetic acid in hot toluene gives 5,5-dimethyl-2-[1-acetyl-2-(3-nitrophenyl)vinyl]-1,3,2-dioxaphosphorina n-2-one (III), which is cyclized with 3-aminocrotonic acid 2(S)-methoxy-2-phenylethyl ester (IV) in refluxing toluene; the recrystallization of the resulting product affords 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4(S)-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 2(S)-methoxy-2-phenylethyl ester (V). The protection of the NH group of (V) with chloromethyl methyl ether and NaH in THF yields the N-methoxymethyl derivative (VI), which is transesterified with 2-(N-benzyl-N-methylamino)ethanol (VII) and NaH in DMSO, giving the protected final product (VIII). Finally, this compound is deprotected with HCl in ethanol.

参考文献中间体

合成目标

【1】 Seto, K.; Matsumoto, H.; Sakoda, R.; Synthesis and crystal structure of optically active 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate (NZ-105). Chem Pharm Bull 1992, 40, 9, 2377.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	12645	5,5-Dimethyl-2-(2-oxopropyl)-1,3,2lambda(5)-dioxaphosphinan-2-one	C₈H₁₅O₄P	详情	详情
(II)	12650	4-[4-Morpholinyl(3-nitrophenyl)methyl]morpholine	C₁₅H₂₁N₃O₄	详情	详情
(III)	12647	2-[(Z)-1-Acetyl-2-(3-nitrophenyl)ethenyl]-5,5-dimethyl-1,3,2lambda(5)-dioxaphosphinan-2-one	C₁₅H₁₈NO₆P	详情	详情
(IV)	12652	(2S)-2-methoxy-2-phenylethyl (E)-3-amino-2-butenoate	C₁₃H₁₇NO₃	详情	详情
(V)	12653	(2S)-2-methoxy-2-phenylethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate	C₂₈H₃₃N₂O₈P	详情	详情
(VI)	12654	(2S)-2-methoxy-2-phenylethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-1-(methoxymethyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate	C₃₀H₃₇N₂O₉P	详情	详情
(VII)	12655	2-(Benzylanilino)-1-ethanol	C₁₅H₁₇NO	详情	详情
(VIII)	12656	2-(benzylanilino)ethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-1-(methoxymethyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate	C₃₆H₄₂N₃O₈P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

An enantioselective synthesis of efonidipine has been described: The enantioselective hydrolysis of 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-n itrophenyl)-1,4-dihydropyridine-3-carboxylic acid propionyloxymethyl ester (I) with lipase AH in 2,5-dimethyltetrahydrofuran saturated with water gives the corresponding free acid of the (S)-isomer (III), while the propionyloxymethyl ester of the (R)-isomer (II) remains undisturbed. After chromatographic separation, the (R)-ester (II) is hydrolyzed with NaOH in methanol to the (R)-acid (IV). Finally, both enantiomerically pure acids (III) and (IV) are separately esterified with 2-(N-benzyl-N-phenylamino)ethanol in the usual way.

参考文献中间体

合成目标

【1】 Ebiike, H.; Achiwa, K.; Yamazaki, Y.; Lipase-catalyzed enantiosynthesis of (R)- and (S)-2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate (NZ 105). Chem Pharm Bull 1995, 43, 7, 1251.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	12657	(propionyloxy)methyl 5-(5,5-dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate	C₂₃H₂₉N₂O₉P	详情	详情
(II)	12658	(propionyloxy)methyl (4R)-5-(5,5-dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate	C₂₃H₂₉N₂O₉P	详情	详情
(III)	12659	(4S)-5-(5,5-Dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid	C₁₉H₂₃N₂O₇P	详情	详情
(IV)	63469	(4R)-5-(5,5-dimethyl-2-oxo-1,3,2lambda~5~-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid	C₁₉H₂₃N₂O₇P	详情	详情
(V)	12655	2-(Benzylanilino)-1-ethanol	C₁₅H₁₇NO	详情	详情

Extended Information