1-bromo-4-phenyl-2-butanone -Drug Synthesis Database

【结构式】

【分子编号】29211

【品名】1-bromo-4-phenyl-2-butanone

【CA登记号】

【分子式】C₁₀H₁₁BrO

【分子量】227.10074

【元素组成】C 52.89% H 4.88% Br 35.18% O 7.05%

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：(II)

The required phosphonate reagent (IV) was prepared by two alternative methods. Bromination of benzylacetone (I) in cold methanol afforded 1-bromo-4-phenyl-2-butanone (II). Subsequent displacement of the bromide ion of (II) with NaI in acetone led to the iodo ketone (III). The desired phosphonate (IV) was then obtained by the Arbuzov reaction of (III) with trimethyl phosphite. Alternatively, alkylation of the dianion of dimethyl 2-oxopropyl phosphonate (V) with benzyl bromide led to phosphonate (IV).

参考文献中间体

合成目标

【1】 Gutman, A.; Nisnevich, G.; Etinger, M.; Zaltzman, I.; Judovich, L.; Pertsikov, B.; A new process for the preparation of latanoprost. WO 0155101 .
【2】 Resul, B.; et al.; Phenyl-substituted prostaglandins: Potent and selective antiglaucoma agents. J Med Chem 1993, 36, 2, 243.

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)	32061	4-phenyl-2-butanone	2550-26-7	C₁₀H₁₂O	详情	详情
(II)	29211	1-bromo-4-phenyl-2-butanone		C₁₀H₁₁BrO	详情	详情
(III)	59557	1-iodo-4-phenyl-2-butanone		C₁₀H₁₁IO	详情	详情
(IV)	59558	dimethyl 2-oxo-4-phenylbutylphosphonate		C₁₂H₁₇O₄P	详情	详情
(V)	59559	Dimethyl acetonylphosphonate; Acetylmethylphosphonic acid dimethyl ester; Dimethyl (2-oxopropyl)phosphonate	4202-14-6	C₅H₁₁O₄P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Reaction of 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (I) with trimethylsilyl cyanide in the presence of boron trifluoride gave nitrile (II), which was treated with liquid hydrogen sulfide and DMAP to yield thioamide (III). Condensation of this thioamide with bromoketone (IV) in acetonitrile afforded the thiazole derivative (V). Hydrolysis of the benzoate esters of (V) using sodium methoxide in methanol, followed by protection of the resulting 2,3-diol with acetone and triethyl orthoformate produced the corresponding isopropylidene ketal (VI). Treatment of the primary alcohol group of (VI) with sulfamoyl chloride gave rise to the sulfamate ester (VII). Further condensation of (VII) with N-Boc-L-leucine furnished (IX). The Boc and isopropylidene groups of (IX) were finally eliminated with trifluoroacetic acid to provide the title compound.

参考文献中间体

合成目标

【1】 Wang, W.; Gallant, P.; Hill, J.M.; Yu, G.; Wendler, P.; Kluge, A.F.; Yu, X.Y.; Synthesis and structure-activity relationships of a series of novel thiazoles as inhibitors of aminoacyl-tRNA synthetases. Bioorg Med Chem Lett 1999, 9, 3, 375.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	20984	methyl (Z)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E)-3-oxo-3-(4-propylcyclohexyl)-1-propenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate	C₃₃H₅₂O₇	详情	详情
(II)	29143	(2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate	C₂₇H₂₁NO₇	详情	详情
(III)	29144	(2R,3S,4R,5R)-2-(aminocarbothioyl)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate	C₂₇H₂₃NO₇S	详情	详情
(IV)	29211	1-bromo-4-phenyl-2-butanone	C₁₀H₁₁BrO	详情	详情
(V)	29212	[(2R,3R,4S,5R)-3,4-bis(benzoyloxy)-5-(4-phenethyl-1,3-thiazol-2-yl)tetrahydro-2-furanyl]methyl benzoate	C₃₇H₃₁NO₇S	详情	详情
(VI)	29213	[(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol	C₁₉H₂₃NO₄S	详情	详情
(VII)	29214	[(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methylsulfamate	C₁₉H₂₄N₂O₆S₂	详情	详情
(VIII)	23663	(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine	C₁₁H₂₁NO₄	详情	详情
(IX)	29215	tert-butyl (1S)-1-[[([[(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methoxy]sulfonyl)amino]carbonyl]-3-methylbutylcarbamate	C₃₀H₄₃N₃O₉S₂	详情	详情

Extended Information