2-(bromomethyl)-1,3-difluorobenzene -Drug Synthesis Database

【结构式】

【分子编号】22316

【品名】2-(bromomethyl)-1,3-difluorobenzene

【CA登记号】85118-00-9

【分子式】C₇H₅BrF₂

【分子量】207.0175064

【元素组成】C 40.61% H 2.43% Br 38.6% F 18.35%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(V)

2-Methyl-6-nitroaniline (I) was acylated with 2,6-difluorobenzoyl chloride (II) to afford the nitroanilide (III). Reduction of the nitro group of (III) with concomitant cyclization using iron powder in refluxing HOAc furnished the benzimidazole (IV). Finally, N-alkylation of (IV) with 2,6-difluoro-alpha-bromotoluene (V) in the presence of NaH provided the title compound.

参考文献中间体

合成目标

【1】 Morningstar, M.; Roth, T.; Michejda, C.J. (US Department of Health & Human Services); Substd. benzimidazoles as non-nucleoside inhibitors of reverse transcriptase. WO 0114343 .

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)	46329	2-methyl-6-nitroaniline; 2-methyl-6-nitrophenylamine		C₇H₈N₂O₂	详情	详情
(II)	46330	2,6-difluorobenzoyl chloride		C₇H₃ClF₂O	详情	详情
(III)	46331	2,6-difluoro-N-(2-methyl-6-nitrophenyl)benzamide		C₁₄H₁₀F₂N₂O₃	详情	详情
(IV)	46332	2-(2,6-difluorophenyl)-4-methyl-1H-benzimidazole		C₁₄H₁₀F₂N₂	详情	详情
(V)	22316	2-(bromomethyl)-1,3-difluorobenzene	85118-00-9	C₇H₅BrF₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

3',4'-Dihydroxyacetophenone (I) was selectively alkylated at position 4' with alpha-bromo-2,6-difluorotoluene (II) in the presence of Li2CO3 in DMF. The resulting ether (III) was further alkylated with ethyl bromoacetate (IV) to give (V). Subsequent Horner-Emmons condensation of (V) with the phosphonoacetamide (VI) provided cinnamide (VII). The target carboxylic acid was then obtained by saponification of the ethyl ester of (VII) with NaOH.

参考文献中间体

合成目标

【1】 Greenspan, P.D.; Fujimoto, R.A.; Marshall, P.J.; Raychaudhuri, A.; Lipson, K.E.; Zhou, H.; Doti, R.A.; Coppa, D.E.; Zhu, L.; Pelletier, R.; Uziel-Fusi, S.; Jackson, R.H.; Chin, M.H.; Kotyuk, B.L.; Fitt, J.J.; Carboxy-substituted cinnamides: A novel series of potent, orally active LTB4 receptor antagonists. J Med Chem 1999, 42, 1, 164.

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)	22315	1-(3,4-dihydroxyphenyl)-1-ethanone	1197-09-7	C₈H₈O₃	详情	详情
(II)	22316	2-(bromomethyl)-1,3-difluorobenzene	85118-00-9	C₇H₅BrF₂	详情	详情
(III)	22317	1-[4-[(2,6-difluorobenzyl)oxy]-3-hydroxyphenyl]-1-ethanone		C₁₅H₁₂F₂O₃	详情	详情
(IV)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(V)	22319	ethyl 2-[5-acetyl-2-[(2,6-difluorobenzyl)oxy]phenoxy]acetate		C₁₉H₁₈F₂O₅	详情	详情
(VI)	22320	diethyl 2-(diethylamino)-2-oxoethylphosphonate		C₁₀H₂₂NO₄P	详情	详情
(VII)	22321	ethyl 2-[5-[(E)-3-(diethylamino)-1-methyl-3-oxo-1-propenyl]-2-[(2,6-difluorobenzyl)oxy]phenoxy]acetate		C₂₅H₂₉F₂NO₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Simultaneous bromination and esterification of 2'-hydroxyphenylacetic acid (I) using tetrabutylammonium tribromide in EtOH at r.t. afforded (II), which was O-alkylated with alpha-bromo-2,6-difluorotoluene (III) in the presence of K2CO3 in refluxing acetone to yield ether (IV). Subsequent Heck olefination of (IV) with diethyl crotonamide (V) in the presence of palladium acetate and tri-o-tolylphosphine provided cinnamide (VI). The target carboxylic acid was then obtained by saponification of the ethyl ester of (VI) with NaOH.

参考文献中间体

合成目标

【1】 Greenspan, P.D.; Fujimoto, R.A.; Marshall, P.J.; Raychaudhuri, A.; Lipson, K.E.; Zhou, H.; Doti, R.A.; Coppa, D.E.; Zhu, L.; Pelletier, R.; Uziel-Fusi, S.; Jackson, R.H.; Chin, M.H.; Kotyuk, B.L.; Fitt, J.J.; Carboxy-substituted cinnamides: A novel series of potent, orally active LTB4 receptor antagonists. J Med Chem 1999, 42, 1, 164.

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)	22322	2-(2-hydroxyphenyl)acetic acid	614-75-5	C₈H₈O₃	详情	详情
(II)	22323	ethyl 2-(5-bromo-2-hydroxyphenyl)acetate		C₁₀H₁₁BrO₃	详情	详情
(III)	22316	2-(bromomethyl)-1,3-difluorobenzene	85118-00-9	C₇H₅BrF₂	详情	详情
(IV)	22325	ethyl 2-[5-bromo-2-[(2,6-difluorobenzyl)oxy]phenyl]acetate		C₁₇H₁₅BrF₂O₃	详情	详情
(V)	22326	(E)-N,N-diethyl-2-butenamide		C₈H₁₅NO	详情	详情
(VI)	22327	ethyl 2-[5-[(E)-3-(diethylamino)-1-methyl-3-oxo-1-propenyl]-2-[(2,6-difluorobenzyl)oxy]phenyl]acetate		C₂₅H₂₉F₂NO₄	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Kankan RN, Rao DR, Birari DR.2010.Process for the preparation of Rufinamide. WO 2010/043849 A1.

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)	22316	2-(bromomethyl)-1,3-difluorobenzene	85118-00-9	C₇H₅BrF₂	详情	详情
(II)	41769	2,6-difluorobenzyl azide; 2-(azidomethyl)-1,3-difluorobenzene		C₇H₅F₂N₃	详情	详情
(III)	41774	methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate		C₁₁H₉F₂N₃O₂	详情	详情

Extended Information