1,1,1-trifluoroacetone -Drug Synthesis Database

【结构式】

【分子编号】35449

【品名】1,1,1-trifluoroacetone

【CA登记号】421-50-1

【分子式】C₃H₃F₃O

【分子量】112.0514296

【元素组成】C 32.16% H 2.7% F 50.87% O 14.28%

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：(X)

The cyclization of trifluoroacetylmethylpyridinium bromide (I) with 3-(4-trifluoromethylbenzoyl)acrylic acid (II) by means of ammonium acetate in refluxing methanol gives 2-trifluoromethyl-6-(4-trifluoromethylphenyl)isonicotinic acid (III), which by condensation with 2-bromopyridine (IV) by means of butyllithium in ethyl ether yields 2-trifluoromethyl-6-(4-trifluoromethylphenyl)4-pyridyl-2'-pyridyl ketone (V). Finally, this compound is reduced with H2 over Pt in aqueous concentrated HCl. The starting products are prepared as follows: 1) The acrylic acid (II) is obtained by condensation of maleic anhydride (VI) with 4-trifluoromethylphenylmagnesium bromide (VII) by means of ZnCl2 in refluxing ethyl ether. An alternative method is the condensation of 4-trifluoromethylacetophenone (VIII) with glyoxylic acid (IX) by means of triethylamine at 135 C. 2) The pyridinium salt (I) is prepared by bromination of 1,1,1-trifluoroacetone (X) giving 1,1,1-trifluoro-3-bromoacetone (XI), which is then condensed with pyridine.

参考文献中间体

合成目标

【1】 La Montagne, M.P.; et al.; Antimalarials. 6. Synthesis, antimalarial activity and configurations of rracemic alpha-(2-piperidyl)-4-pyridinemethanols. J Med Chem 1974, 17, 5, 219-523.
【2】 Ash, A.B.; et al. (Department of the Army); 2-Substituted phenyl-6-trifluoromethyl-4-pyridylcarbinolamines. US 3940404 .
【3】 Ash, A.B.; et al. (Department of the Army); 2-Aryl-6-trifluoromethyl-4-pyridylcarbinolamine antimalarials. US 3953463 .
【4】 Ash, A.B.; et al. (Department of the Army); 2-Aryl-6-trifluoromethyl-4-pyridylcarbinolamine antimalarials. US 3886167 .
【5】 Castaner, J.; Roberts, P.J.; WR-180,409. Drugs Fut 1978, 3, 9, 694.

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)	39908	1-(3,3,3-trifluoro-2-oxopropyl)pyridinium bromide		C₈H₇BrF₃NO	详情	详情
(II)	39906	(E)-4-oxo-4-[4-(trifluoromethyl)phenyl]-2-butenoic acid		C₁₁H₇F₃O₃	详情	详情
(III)	39910	2-(trifluoromethyl)-6-[4-(trifluoromethyl)phenyl]isonicotinic acid		C₁₄H₇F₆NO₂	详情	详情
(IV)	29052	2-Bromopyridine；α-bromopyridine;α-bromoazine	109-04-6	C₅H₄BrN	详情	详情
(V)	39911	2-pyridinyl[2-(trifluoromethyl)-6-[4-(trifluoromethyl)phenyl]-4-pyridinyl]methanone		C₁₉H₁₀F₆N₂O	详情	详情
(VI)	11182	2,5-Furandione; Maleic anhydride	108-31-6	C₄H₂O₃	详情	详情
(VII)	39311	bromo[4-(trifluoromethyl)phenyl]magnesium		C₇H₄BrF₃Mg	详情	详情
(VIII)	39907	1-[4-(trifluoromethyl)phenyl]-1-ethanone	709-63-7	C₉H₇F₃O	详情	详情
(IX)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(X)	35449	1,1,1-trifluoroacetone	421-50-1	C₃H₃F₃O	详情	详情
(XI)	39909	3-bromo-1,1,1-trifluoroacetone	431-35-6	C₃H₂BrF₃O	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 bromination of 1,1,1-trifluoroacetone (I) according to McBee and Burton gives 3,3-dibromo-1,1,1-trifluoroacetone (II), which is hydrolyzed with aqueous NaOAc to the glyoxal (III). The cyclization of (III) with benzaldehyde (IV) and ammonia in methanol yields 2-phenyl-4-(trifluoromethyl)-1H-imidazole (V), which is converted into the carbonitrile (VI) by reaction with hot aqueous ammonium hydroxide. The reduction of (VI) with diisobutylaluminum hydride in THF affords the carbaldehyde (VII), which is finally condensed with N-tert-butylhydroxylamine (VIII) by means of NaHCO3 in hot ethanol.

参考文献中间体

合成目标

【1】 Dhainaut, A.; et al.; Synthesis, structure, and neuroprotective properties of novel imidazolyl nitrones. J Med Chem 2000, 43, 11, 2165.
【2】 Dhainaut, A.; Lestage, P.; Lockhart, B.; Tizot, A.; Goldstein, S. (ADIR et Cie.); Nitrone derivs., process for their preparation and pharmaceutical compsns. containing them. CA 2274621; EP 0967207; FR 2780404; JP 2000026428; US 6034250 .

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)	35449	1,1,1-trifluoroacetone	421-50-1	C₃H₃F₃O	详情	详情
(II)	35450	3,3-dibromo-1,1,1-trifluoroacetone	431-67-4	C₃HBr₂F₃O	详情	详情
(III)	35451	3,3,3-trifluoro-2-oxopropanal		C₃HF₃O₂	详情	详情
(IV)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(V)	35452	2-phenyl-4-(trifluoromethyl)-1H-imidazole		C₁₀H₇F₃N₂	详情	详情
(VI)	35435	(1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,4,6,7,9,11-hexamethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate		C₄₆H₄₂O₁₂	详情	详情
(VII)	35454	2-phenyl-1H-imidazole-4-carbaldehyde		C₁₀H₈N₂O	详情	详情
(VIII)	35455	N-(tert-butyl)hydroxylamine; 2-(hydroxyamino)-2-methylpropane		C₄H₁₁NO	详情	详情

Extended Information