1-bromo-4-phenoxybenzene; 4-bromophenyl phenyl ether -Drug Synthesis Database

【结构式】

【分子编号】35580

【品名】1-bromo-4-phenoxybenzene; 4-bromophenyl phenyl ether

【CA登记号】101-55-3

【分子式】C₁₂H₉BrO

【分子量】249.10686

【元素组成】C 57.86% H 3.64% Br 32.08% O 6.42%

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)

Chlorosulfonation of 4-bromodiphenyl ether (I) in cold CH2Cl2 afforded the corresponding sulfonyl chloride (II). After silylation of D-tert-leucine (III) with chlorotrimethylsilane and N-methylmopholine, coupling with acid chloride (II) provided sulfonamide (IV). Conversion of (IV) to acid chloride (V) was then achieved by treatment with oxalyl chloride and a catalytic amount of DMF at low temperature. Finally, condensation of (V) with hydroxylamine in aqueous THF gave rise to the target hydroxamic acid.

参考文献中间体

合成目标

【1】 Abreo, M.A.; Bender, S.L. (Agouron Pharmaceuticals, Inc.); Metalloproteinase inhibitors, pharmaceutical compsns. containing them and their pharmaceutical uses. EP 0973748; WO 9843963 .

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)	35580	1-bromo-4-phenoxybenzene; 4-bromophenyl phenyl ether	101-55-3	C₁₂H₉BrO	详情	详情
(II)	35579	4-(4-bromophenoxy)benzenesulfonyl chloride		C₁₂H₈BrClO₃S	详情	详情
(III)	35583	(2R)-2-amino-3,3-dimethylbutyric acid; D-tert-Leucine	26782-71-8	C₆H₁₃NO₂	详情	详情
(IV)	35581	(2R)-2-([[4-(4-bromophenoxy)phenyl]sulfonyl]amino)-3,3-dimethylbutyric acid		C₁₈H₂₀BrNO₅S	详情	详情
(V)	35582	(2R)-2-([[4-(4-bromophenoxy)phenyl]sulfonyl]amino)-3,3-dimethylbutanoyl chloride		C₁₈H₁₉BrClNO₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Addition of the Grignard reagent prepared from 4-bromodiphenyl ether (I) to N-Boc-4-piperidone (II) gave the 4-hydroxy-4-arylpiperidine (III). Deprotection of the Boc group of (III) with concomitant dehydration of the tertiary alcohol by means of trifluoroacetic acid afforded the tetrahydropyridine (IV), which was further hydrogenated to piperidine (V) using Pd/C as the catalyst. Condensation of pieridine (V) with phenyl glycidyl ether (VI) in refluxing isopropanol yielded the desired amino alcohol, which was finally isolated as the corresponding hydrochloride salt.

参考文献中间体

合成目标

【1】 Nakanishi, K.; Miyajima, A.; Annoura, H.; Uesugi, M.; Fukunaga, A.; Tamura, S.; Tamura-Horikawa, Y.; A novel class of Na+ and Ca2+ channel dual blockers with highly potent anti-ischemic effects. Bioorg Med Chem Lett 1999, 9, 20, 2999.

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)	35580	1-bromo-4-phenoxybenzene; 4-bromophenyl phenyl ether	101-55-3	C₁₂H₉BrO	详情	详情
(II)	18620	tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone	79099-07-3	C₁₀H₁₇NO₃	详情	详情
(III)	40680	tert-butyl 4-hydroxy-4-(4-phenoxyphenyl)-1-piperidinecarboxylate		C₂₂H₂₇NO₄	详情	详情
(IV)	40681	phenyl 4-(1,2,3,6-tetrahydro-4-pyridinyl)phenyl ether; 4-(4-phenoxyphenyl)-1,2,3,6-tetrahydropyridine		C₁₇H₁₇NO	详情	详情
(V)	40682	phenyl 4-(4-piperidinyl)phenyl ether; 4-(4-phenoxyphenyl)piperidine		C₁₇H₁₉NO	详情	详情
(VI)	23932	2-(phenoxymethyl)oxirane; oxiranylmethyl phenyl ether	122-60-1	C₉H₁₀O₂	详情	详情

Extended Information