3-hydroxy-2,2-dimethylpropanal -Drug Synthesis Database

【结构式】

【分子编号】63266

【品名】3-hydroxy-2,2-dimethylpropanal

【CA登记号】

【分子式】C₅H₁₀O₂

【分子量】102.1332

【元素组成】C 58.8% H 9.87% O 31.33%

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：(V)

The optically active amino benzhydrol (I) is acylated with dimethylmalonyl chloride monoethyl ester (II) to yield amide (III). Subsequent reduction of the amide-ester (III) by means of LiAlH4 furnishes amino alcohol (IV). Alternatively, the intermediate amino alcohol (IV) is prepared by reductive alkylation of (I) with 3-hydroxy-2,2-dimethylpropionaldehyde (V) in the presence of NaBH3CN. Condensation of (IV) with fumaryl chloride monoethyl ester (VI) provides amide (VII). Intramolecular cyclization of the conjugated carboxamide (VII) in the presence of K2CO3 leads to the benzoxazepine derivative (VIII). The ethyl ester group of (VIII) is then hydrolyzed under alkaline conditions to furnish acid (IX).

参考文献中间体

合成目标

【1】 Miki, T.; Kori, M.; Mabuchi, H.; Tozawa, R.; Nishimoto, T.; Sugiyama, Y.; Teshima, K.; Yukimasa, H.; Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis. J Med Chem 2002, 45, 20, 4571.
【2】 Yukimasa, H.; Sugiyama, Y.; Tozawa, R. (Takeda Chemical Industries, Ltd.); Benzoxazepine cpds., their production and use as lipid lowering agents. EP 0862562; EP 1097928; JP 1997136880; JP 2001097963; US 6110909; US 6613761; WO 9710224 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63258	(S)-(2-amino-5-chlorophenyl)(2,3-dimethoxyphenyl)methanol	C₁₅H₁₆ClNO₃	详情	详情
(II)	63259	ethyl 3-chloro-2,2-dimethyl-3-oxopropanoate	C₇H₁₁ClO₃	详情	详情
(III)	63260	ethyl 3-{4-chloro-2-[(S)-(2,3-dimethoxyphenyl)(hydroxy)methyl]anilino}-2,2-dimethyl-3-oxopropanoate	C₂₂H₂₆ClNO₆	详情	详情
(IV)	63261	3-{4-chloro-2-[(S)-(2,3-dimethoxyphenyl)(hydroxy)methyl]anilino}-2,2-dimethyl-1-propanol	C₂₀H₂₆ClNO₄	详情	详情
(V)	63266	3-hydroxy-2,2-dimethylpropanal	C₅H₁₀O₂	详情	详情
(VI)	63262	ethyl (E)-4-chloro-4-oxo-2-butenoate	C₆H₇ClO₃	详情	详情
(VII)	63263	ethyl (E)-4-[4-chloro-2-[(S)-(2,3-dimethoxyphenyl)(hydroxy)methyl](3-hydroxy-2,2-dimethylpropyl)anilino]-4-oxo-2-butenoate	C₂₆H₃₂ClNO₇	详情	详情
(VIII)	63264	ethyl 2-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetate	C₂₆H₃₂ClNO₇	详情	详情
(IX)	63265	2-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetic acid	C₂₄H₂₈ClNO₇	详情	详情

Extended Information