bis(4-bromophenyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】34447

【品名】bis(4-bromophenyl)methanone

【CA登记号】3988-03-2

【分子式】C₁₃H₈Br₂O

【分子量】340.01392

【元素组成】C 45.92% H 2.37% Br 47% O 4.71%

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：(IV)

Addition of lithium trimethylsilylacetylide (II) to quinuclidin-3-one (I) in THF at -70 C afforded the O-silylated ethynyl quinuclidinol (III). Subsequent palladium-catalyzed coupling of (III) with 4,4'-dibromobenzophenone (IV) gave adduct (V). Finally, the Meyer-Schuster rearrangement of (V) in concentrated H2SO4 furnished the title unsaturated ketone.

参考文献中间体

合成目标

【1】 Brown, G.R.; Stokes, E.S.E.; Hollinshead, D.M.; et al.; Quinuclidine inhibitors of 2,3-oxidosqualene cyclase-lanosterol synthase: Optimization from lipid profiles. J Med Chem 1999, 42, 7, 1306.

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)	16925	3-quinuclidinone; 1-azabicyclo[2.2.2]octan-3-one	1193-65-3	C₇H₁₁NO	详情	详情
(II)	16299	Lithium (trimethylsilyl)acetylide; [2-(Trimethylsilyl)ethynyl]lithium	54655-07-1	C₅H₉LiSi	详情	详情
(III)	34446	3-ethynyl-3-[(trimethylsilyl)oxy]quinuclidine; 3-ethynyl-1-azabicyclo[2.2.2]oct-3-yl trimethylsilyl ether		C₁₂H₂₁NOSi	详情	详情
(IV)	34447	bis(4-bromophenyl)methanone	3988-03-2	C₁₃H₈Br₂O	详情	详情
(V)	34448	(4-bromophenyl)[4-(2-[3-[(trimethylsilyl)oxy]-1-azabicyclo[2.2.2]oct-3-yl]ethynyl)phenyl]methanone		C₂₅H₂₈BrNO₂Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The Horner-Emmons condensation of 4,4'-dibromobenzophenone (I) with triethyl phosphonoacetate leads to the 3,3-diarylpropenoate (II). Ester (II) is subsequently reduced to the allylic alcohol (III) employing DIBAL in cold THF. Suzuki coupling of aryl bromide (III) with phenylboronic acid (IV) furnishes 3,3-bis-(biphenyl-4-yl)-2-propen-1-ol (V). Coupling of allylic alcohol (V) with (S) ethyl 2-ethoxy-3-(4-hydroxyphenyl)propionate (VI) by means of 1,1'-(azodicarbonyl)dipiperidine (ADDP) and tributylphosphine under Mitsunobu conditions gives rise to the ether adduct (VII). Finally, saponification of the ethyl ester group of (VII) provides the target carboxylic acid.

参考文献中间体

合成目标

【1】 Mogensen, J.P.; Jeppesen, L.; Bury, P.S.; Pettersson, I.; Fleckner, J.; Nehlin, J.; Frederiksen, K.S.; Albrektsen, T.; Din, N.; Mortensen, S.B.; Svensson, L.A.; Wasserman, K.; Wulff, E.M.; Ynddal, L.; Sauerberg, P.; Design and synthesis of novel PPARalpha/gamma/delta triple activators using a known PPARalpha/gamma dual activator as structural template. Bioorg Med Chem Lett 2003, 13, 2, 257.
【2】 Sauerberg, P.; Jeppesen, L.; Bury, P.S.; Murray, A.; Pettersson, I. (Novo Nordisk A/S); New cpds., their preparation and use. EP 1171414; JP 2002542218; WO 0063153 .

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)	34447	bis(4-bromophenyl)methanone	3988-03-2	C₁₃H₈Br₂O	详情	详情
(II)	63223	ethyl 3,3-bis(4-bromophenyl)acrylate		C₁₇H₁₄Br₂O₂	详情	详情
(III)	63224	3,3-bis(4-bromophenyl)-2-propen-1-ol		C₁₅H₁₂Br₂O	详情	详情
(IV)	16593	Phenylboronic acid；Benzeneboronic acid;Phenylboron dihydroxide	98-80-6	C₆H₇BO₂	详情	详情
(V)	63225	3,3-di[1,1'-biphenyl]-4-yl-2-propen-1-ol		C₂₇H₂₂O	详情	详情
(VI)	50418	ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate		C₁₃H₁₈O₄	详情	详情
(VII)	63226	ethyl (2S)-3-{4-[(3,3-di[1,1'-biphenyl]-4-yl-2-propenyl)oxy]phenyl}-2-ethoxypropanoate		C₄₀H₃₈O₄	详情	详情

Extended Information