diethyl 2-methyl-2-[4-(2-thienylcarbonyl)phenyl]malonate -Drug Synthesis Database

【结构式】

【分子编号】34019

【品名】diethyl 2-methyl-2-[4-(2-thienylcarbonyl)phenyl]malonate

【CA登记号】

【分子式】C₁₉H₂₀O₅S

【分子量】360.4308

【元素组成】C 63.32% H 5.59% O 22.19% S 8.9%

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：(III)

The reaction of 2-thiophenecarbonyl chloride (I) with fluorobenzene (A) by means of AlCl3 gives (4-fluorophenyl)(2-thienyl)ketone (II), which is then condensed with diethyl methylmalonate (B) by means of NaH in benzene-HMPA to yield diethyl 2-methyl-2-[4-(2-thienylcarbonyl)phenyl]malonate (III); this product is finally hydrolyzed and partially decarboxylated with refluxing aqueous NaOH.

参考文献中间体

合成目标

【1】 Van Daele, P.G.H.; et al.; Synthesis of alpha-methyl-4-(2-thienylcarbonyl)benzene acetic acid, suprofen and derivatives. Arzneim-Forsch Drug Res 1975, 25, 10, 1495-1501.
【2】 Castaner, J.; Chatterjee, S.S.; Suprofen. Drugs Fut 1976, 1, 3, 148.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	17466	Fluorobenzene	462-06-6	C₆H₅F	详情	详情
(B)	30310	diethyl 2-methylmalonate	609-08-5	C₈H₁₄O₄	详情	详情
(I)	14103	2-Thiophenecarbonyl chloride	5271-67-0	C₅H₃ClOS	详情	详情
(II)	34018	(4-fluorophenyl)(2-thienyl)methanone	579-49-7	C₁₁H₇FOS	详情	详情
(III)	34019	diethyl 2-methyl-2-[4-(2-thienylcarbonyl)phenyl]malonate		C₁₉H₂₀O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The reaction of 1-(4-bromophenyl)ethanol (IV) with 3,4-dihydro-2H-pyran (C) by means of HCl yields 2-[1-(4-bromophenyl)ethoxy]tetrahydro-2H-pyran (V); this product by condensation with 2-thiophenecarbonitrile (D) through its Grignard complex in THF gives [4-(1-hydroxyethyl)phenyl](2-thienyl)ketone (VI), which without purification is treated with SOCl2 in benzene to give [4-(1-chloroethyl)phenyl](2-thienyl)ketone (VII); then the halogen is substituted by CN with NaCN in DMSO to afford alpha-methyl-4-(2-thienylcarbonyl)benzeneacetonitrile (VIII), which, without purification, is hydrolyzed with H2SO4 and acetic acid.

参考文献中间体

合成目标

【1】 Van Daele, P.G.H.; et al.; Synthesis of alpha-methyl-4-(2-thienylcarbonyl)benzene acetic acid, suprofen and derivatives. Arzneim-Forsch Drug Res 1975, 25, 10, 1495-1501.
【2】 Castaner, J.; Chatterjee, S.S.; Suprofen. Drugs Fut 1976, 1, 3, 148.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(D)	34025	Thiophene-2-carbonitrile; 2-thiophenecarbonitrile	1003-31-2	C₅H₃NS	详情	详情
(IV)	34019	diethyl 2-methyl-2-[4-(2-thienylcarbonyl)phenyl]malonate		C₁₉H₂₀O₅S	详情	详情
(V)	34021	1-(4-bromophenyl)ethyl tetrahydro-2H-pyran-2-yl ether; 2-[1-(4-bromophenyl)ethoxy]tetrahydro-2H-pyran		C₁₃H₁₇BrO₂	详情	详情
(VI)	34022	[4-(1-hydroxyethyl)phenyl](2-thienyl)methanone		C₁₃H₁₂O₂S	详情	详情
(VII)	34023	[4-(1-chloroethyl)phenyl](2-thienyl)methanone		C₁₃H₁₁ClOS	详情	详情
(VIII)	34024	2-[4-(2-thienylcarbonyl)phenyl]propanenitrile		C₁₄H₁₁NOS	详情	详情
(C)	13684	3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran	110-87-2	C₅H₈O	详情	详情

Extended Information