ethyl 4-bromo-3-thiophenecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】23828

【品名】ethyl 4-bromo-3-thiophenecarboxylate

【CA登记号】

【分子式】C₇H₇BrO₂S

【分子量】235.10138

【元素组成】C 35.76% H 3% Br 33.99% O 13.61% S 13.64%

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 intermediate 4-bromothiophene-3-carboxylic acid (II) was prepared in low yield by lithium-halogen exchange of 3,4-dibromothiophene (I) with n-BuLi in Et2O at -78 C, followed by quenching with solid CO2. Alternatively, lithiation of (I) at -116 C and further quenching with ethyl chloroformate provided ethyl ester (III) in moderate yields, accompanied by some byproducts that were separated by column chromatography. The required carboxylic acid (II) was then formed by saponification of (III) with NaOH. Subsequent condensation of bromoacid (II) with benzoylacetone (IV) either in the presence of sodium ethoxide and copper powder or NaH and CuBr proceeded with concomitant retro-Claisen cleavage to provide monoketone (V). The target thienopyridinone was then obtained by cyclization of (V) with ammonium acetate in refluxing AcOH.

参考文献中间体

合成目标

【1】 Shinkwin, A.E.; et al.; Synthesis of thiophenecarboxamides, thieno[3,4-c]p. Bioorg Med Chem 1999, 7, 2, 297.

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)	23826	3,4-dibromothiophene	3141-26-2	C₄H₂Br₂S	详情	详情
(II)	23827	4-bromo-3-thiophenecarboxylic acid		C₅H₃BrO₂S	详情	详情
(III)	23828	ethyl 4-bromo-3-thiophenecarboxylate		C₇H₇BrO₂S	详情	详情
(IV)	23829	1-phenyl-1,3-butanedione	93-91-4	C₁₀H₁₀O₂	详情	详情
(V)	23830	4-(2-oxo-2-phenylethyl)-3-thiophenecarboxylic acid		C₁₃H₁₀O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The intermediate 4-bromothiophene-3-carboxylic acid (II) was prepared in low yield by lithium-halogen exchange of 3,4-dibromothiophene (I) with n-BuLi in Et2O at -78 C, followed by quenching with solid CO2. Alternatively, lithiation of (I) at -116 C and further quenching with ethyl chloroformate provided ethyl ester (III) in moderate yields, accompanied by some byproducts that were separated by column chromatography. The required carboxylic acid (II) was then formed by saponification of (III) with NaOH. Subsequent condensation of bromoacid (II) with acetylacetone (IV) in the presence of potassium tert-butoxide and copper powder in refluxing tert-butanol provided the thienylpentanedione (V). Deacetylation with aqueous ammonia then gave the monoketone (VI). The target thienopyridinone was finally obtained by cyclization of (VI) with ammonium acetate in refluxing AcOH.

参考文献中间体

合成目标

【1】 Shinkwin, A.E.; et al.; Synthesis of thiophenecarboxamides, thieno[3,4-c]p. Bioorg Med Chem 1999, 7, 2, 297.

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)	23826	3,4-dibromothiophene	3141-26-2	C₄H₂Br₂S	详情	详情
(II)	11620	2,4-Pentanedione;acetylacetone	123-54-6	C₅H₈O₂	详情	详情
(II)	23827	4-bromo-3-thiophenecarboxylic acid		C₅H₃BrO₂S	详情	详情
(III)	23828	ethyl 4-bromo-3-thiophenecarboxylate		C₇H₇BrO₂S	详情	详情
(V)	23832	4-[(Z)-1-acetyl-2-hydroxy-1-propenyl]-3-thiophenecarboxylic acid		C₁₀H₁₀O₄S	详情	详情
(VI)	23833	4-(2-oxopropyl)-3-thiophenecarboxylic acid		C₈H₈O₃S	详情	详情

Extended Information