2-isopropylphenol -Drug Synthesis Database

【结构式】

【分子编号】37653

【品名】2-isopropylphenol

【CA登记号】88-69-7

【分子式】C₉H₁₂O

【分子量】136.19368

【元素组成】C 79.37% H 8.88% O 11.75%

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)

An enantioselective total synthesis of chloride (MOM-Cl) and NaH in THF gives the methoxymethyl ether (II), which is methylated with n-BuLi and methyl iodide in THF yielding the 6-methyl derivative (III). The condensation of (III) with 3-methyl-2-butenyl bromide (IV) by means of s-BuLi in THF affords compound (V), which is deprotected with LiBF4 and TMSCl in acetonitrile to give the phenol (VI). Methylation of (VI) with dimethyl sulfate and K2CO3 in refluxing acetone provides the ether (VII), which is hydroxylated at the terminal methyl group with SeO2 and tert-butyl hydroperoxide (TBHP) in dichloromethane giving alcohol (VIII). The reaction of (VIII) with methanesulfonyl chloride and then with LiBr affords the corresponding alkenyl bromide (IX), which is condensed with methyl acetoacetate (X) by means of NaH and n-BuLi in THF providing the ketoester (XI).

参考文献中间体

合成目标

【1】 Ye, X.-Y.; Yang, D.; Xu, M.; Enantioselective total synthesis of (-)-triptolide, (-)-triptonide, (+)-triptophenolide, and (+)-triptoquinomide. J Org Chem 2000, 65, 7, 2208.

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)	37653	2-isopropylphenol	88-69-7	C₉H₁₂O	详情	详情
(II)	37654	1-isopropyl-2-(methoxymethoxy)benzene; (2-isopropylphenoxy)methyl methyl ether		C₁₁H₁₆O₂	详情	详情
(III)	37655	1-isopropyl-2-(methoxymethoxy)-3-methylbenzene; (2-isopropyl-6-methylphenoxy)methyl methyl ether		C₁₂H₁₈O₂	详情	详情
(IV)	12989	4-Bromo-2-methyl-2-butene; 1-Bromo-3-methyl-2-butene	870-63-3	C₅H₉Br	详情	详情
(V)	37656	1-isopropyl-2-(methoxymethoxy)-3-(4-methyl-3-pentenyl)benzene; [2-isopropyl-6-(4-methyl-3-pentenyl)phenoxy]methyl methyl ether		C₁₇H₂₆O₂	详情	详情
(VI)	37657	2-isopropyl-6-(4-methyl-3-pentenyl)phenol		C₁₅H₂₂O	详情	详情
(VII)	37658	1-isopropyl-2-methoxy-3-(4-methyl-3-pentenyl)benzene; 2-isopropyl-6-(4-methyl-3-pentenyl)phenyl methyl ether		C₁₆H₂₄O	详情	详情
(VIII)	37659	(E)-5-(3-isopropyl-2-methoxyphenyl)-2-methyl-2-penten-1-ol		C₁₆H₂₄O₂	详情	详情
(IX)	37660	2-[(E)-5-bromo-4-methyl-3-pentenyl]-6-isopropylphenyl methyl ether; 1-[(E)-5-bromo-4-methyl-3-pentenyl]-3-isopropyl-2-methoxybenzene		C₁₆H₂₃BrO	详情	详情
(X)	11791	methyl 3-oxobutanoate; Methyl acetoacetate	105-45-3	C₅H₈O₃	详情	详情
(XI)	35414	methyl (E)-9-(3-isopropyl-2-methoxyphenyl)-6-methyl-3-oxo-6-nonenoate		C₂₁H₃₀O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reaction of 2-isopropylphenol (I) first with NaNO2/AcOH, then with Na2S2O4 and finally with acetic anhydride gives the acetamide (II), which is treated with formaldehyde and tert-butylamine in ethanol yielding the tert-butylaminomethyl derivative (III). The hydrolysis of (III) with 6M HCl affords the aminophenol (IV), which is finally condensed with 4,7-dichloroquinoline (V) in refluxing ethanol.

参考文献中间体

合成目标

【1】 Raynes, K.J.; Stocks, P.A.; Ward, S.A.; O'Neill, P.M.; Park, B.K.; New 4-aminoquinoline mannich base antimalarials. 1. Effect of an alkyl substituent in the 5'-position of the 4'-hydroxyanilino side chain. J Med Chem 1999, 42, 15, 2747.

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)	37653	2-isopropylphenol	88-69-7	C₉H₁₂O	详情	详情
(II)	38278	N-(4-hydroxy-3-isopropylphenyl)acetamide		C₁₁H₁₅NO₂	详情	详情
(III)	38279	N-[3-[(tert-butylamino)methyl]-4-hydroxy-5-isopropylphenyl]acetamide		C₁₆H₂₆N₂O₂	详情	详情
(IV)	38280	4-amino-2-[(tert-butylamino)methyl]-6-isopropylphenol		C₁₄H₂₄N₂O	详情	详情
(V)	38277	4,7-dichloroquinoline	86-98-6	C₉H₅Cl₂N	详情	详情

Extended Information