2-bromo-1-(4-fluorophenyl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】27904

【品名】2-bromo-1-(4-fluorophenyl)-1-ethanone

【CA登记号】403-29-2

【分子式】C₈H₆BrFO

【分子量】217.0374432

【元素组成】C 44.27% H 2.79% Br 36.82% F 8.75% O 7.37%

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)

A synthesis of [14C]-labeled fluvastatin has been described: The acylation of fluorobenzene (I) with [14C]-bromoacetyl chloride (II) by means of AlCl3 gives the expected phenacyl bromide (III), which is condensed with N-isopropylaniline (IV) in hot ethanol yielding the tertiary amine (V). The cyclization of (V) by means of anhydrous ZnCl2 in refluxing ethanol affords the indole (VI), which is alkylated with 3-(N-methyl-N-phenylamino)acroleine (VII) by means of POCl3 in refluxing acetonitrile giving 3-[3-(4-fluorophenyl)-1-isopropylindol-2-yl]acroleine (VIII). The reductocondensation of (VIII) with tert-butyl acetoacetate (IX) by means of NaH and BuLi in THF yields 7-[3-(4-fluorophenyl)-1-isopropylindol-2-yl)-5-hydroxy-3-oxo-6-heptenoic acid tert-butyl ester (X), which is further reduced with NaBH4 and diethyl(methoxy)borane in THF to the dihydroxy compound (XI) as a mixture of the two syn-enantiomers (XI). Finally, this compound is hydrolyzed with NaOH in methanol to the expected sodium salt.

参考文献中间体

合成目标

【1】 Jones, L.; Tang, Y.S.; Sunay, U.B.; Synthesis of carbon-14 labeled fluvastatin (Lescol(R)). J Label Compd Radiopharm 1998, 41, 1, 1.

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)	17466	Fluorobenzene	462-06-6	C₆H₅F	详情	详情
(II)	27903	2-Bromoacetyl chloride	22118-09-8	C₂H₂BrClO	详情	详情
(II)	45080	2-bromoacetyl chloride		C₂H₂BrClO	详情	详情
(III)	27904	2-bromo-1-(4-fluorophenyl)-1-ethanone	403-29-2	C₈H₆BrFO	详情	详情
(III)	45081	2-bromo-1-(4-fluorophenyl)-1-ethanone		C₈H₆BrFO	详情	详情
(IV)	27905	N-isopropyl-N-phenylamine	768-52-5	C₉H₁₃N	详情	详情
(V)	11787	1-(4-Fluorophenyl)-2-(isopropylanilino)-1-ethanone		C₁₇H₁₈FNO	详情	详情
(V)	45082	1-(4-fluorophenyl)-2-(isopropylanilino)-1-ethanone		C₁₇H₁₈FNO	详情	详情
(VI)	11788	3-(4-Fluorophenyl)-1-isopropyl-1H-indole	93957-49-4	C₁₇H₁₆FN	详情	详情
(VI)	45083	3-(4-fluorophenyl)-1-isopropyl-1H-indole		C₁₇H₁₆FN	详情	详情
(VII)	27906	(E)-3-(methylanilino)-2-propenal		C₁₀H₁₁NO	详情	详情
(VIII)	11790	(E)-3-[3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl]-2-propenal		C₂₀H₁₈FNO	详情	详情
(VIII)	45084	(E)-3-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-2-propenal		C₂₀H₁₈FNO	详情	详情
(IX)	27907	Acetoacetic acid tert-butyl ester;3-Oxo-butanoic acid 1,1-dimethylethyl estertert-butyl 3-oxobutanoate	1694-31-1	C₈H₁₄O₃	详情	详情
(X)	27908	tert-butyl (E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-5-hydroxy-3-oxo-6-heptenoate		C₂₈H₃₂FNO₄	详情	详情
(X)	45085	tert-butyl (E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-5-hydroxy-3-oxo-6-heptenoate		C₂₈H₃₂FNO₄	详情	详情
(XI)	27909	tert-butyl (3R,5S,6E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3,5-dihydroxy-6-heptenoate		C₂₈H₃₄FNO₄	详情	详情
(XI)	45086	tert-butyl (3R,5S,6E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3,5-dihydroxy-6-heptenoate		C₂₈H₃₄FNO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The (phenylsulfanyl)piperidine (III) was obtained by condensation of N-Boc-4-piperidinol (I) with diphenyl disulfide (II) in the presence of tributylphosphine. Subsequent oxidation of sulfide (III) to the corresponding sulfone (IV) was achieved using oxone® on wet alumina. Deprotection of the N-Boc-piperidine (IV) with HCl afforded piperidine (V), which was finally alkylated with 2-bromo-4'-fluoroacetophenone (VI) to furnish the title N-phenacyl piperidine.

参考文献中间体

合成目标

【1】 Blurton, P.; Burkamp, F.; Fletcher, S.R.; et al.; 4-(Phenylsulfonyl)piperidines: Novel, selective, and biovailable 5-HT2A receptor antagonists. J Med Chem 2002, 45, 2, 492.
【2】 Macleod, A.M.; Blurton, P.; Fletcher, S.R.; Van Niel, M.B.; Burkamp, F.; Cheng, S.K.-F. (Merck Sharp & Dohme Ltd.); Phenylsulphonyl derivs. as 5-HT receptor ligands. EP 1147083; WO 0043362 .

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)	18625	tert-butyl 4-hydroxy-1-piperidinecarboxylate		C₁₀H₁₉NO₃	详情	详情
(II)	17473	diphenyl disulfide; 1-(phenyldisulfanyl)benzene; diphenyldisulfide	882-33-7	C₁₂H₁₀S₂	详情	详情
(III)	32561	tert-butyl 4-(phenylsulfanyl)-1-piperidinecarboxylate		C₁₆H₂₃NO₂S	详情	详情
(IV)	56311	tert-butyl 4-(phenylsulfonyl)-1-piperidinecarboxylate		C₁₆H₂₃NO₄S	详情	详情
(V)	56312	4-(phenylsulfonyl)piperidine; phenyl 4-piperidinyl sulfone		C₁₁H₁₅NO₂S	详情	详情
(VI)	27904	2-bromo-1-(4-fluorophenyl)-1-ethanone	403-29-2	C₈H₆BrFO	详情	详情

Extended Information