78-77-3Relevant academic research and scientific papers
New preparation method of febuxostat intermediate
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Paragraph 0098-0100, (2020/03/06)
The invention relates to a new preparation method of a febuxostat intermediate. The method includes: taking cheap 4-hydroxybenzaldehyde as an initial raw material, firstly preparing aldoxime from 4-hydroxybenzaldehyde and hydroxylamine hydrochloride, then adding a corresponding thio reagent, and preparing a compound 4-hydroxythiobenzamide (152A1-00) by Beckmann rearrangement reaction; utilizing one-pot process, adopting cheap 4-hydroxybenzaldehyde as an initial raw material, carrying out a series of reactions, and then performing cyclization with 2-halogenated ethyl acetoacetate to obtain ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate or different salt forms (152A2x) thereof; and using isobutyl sulfonate (152H1x) with more easily controllable quality to replace bromo-isobutane soas to prepare ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate (152A4-00). In conclusion, the method provided by the invention is more beneficial to safe, simple and cost-efficientindustrial scale preparation of the febuxostat intermediate with higher purity.
PROCESSES FOR MAKING ALKYL HALIDES
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Page/Page column 8, (2010/09/18)
The invention is directed to processes for producing an alkyl halide, preferably isobutyl bromide. In one embodiment, the process comprises the steps of: (a) contacting an alcohol with a hydrogen halide in a reactor at elevated temperature under conditions effective to form an initial product mixture comprising the alkyl halide, the alcohol, the hydrogen halide and water; (b) cooling the initial product mixture to form a cooled organic phase positioned above a cooled aqueous phase; (c) separating the cooled organic phase from the cooled aqueous phase. The process preferably further comprises a step of: (d) heating at least a portion of the cooled aqueous phase under conditions effective to form additional alkyl halide.
Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
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, (2008/06/13)
This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
Kinetics and thermochemistry of the R + HBr ? RH + Br (R = n-C3H7, isoC3H7, n-C4H9, isoC4H9, sec-C4H9 or tert-C4H9) equilibrium
Seetula, Jorma A.,Slagle, Irene R.
, p. 1709 - 1719 (2007/10/03)
The kinetics of the reactions of n-C3H7, isoC3H7, n-C4H9, isoC4H9, sec-C4H9 and tert-C4H9 radicals, R, with HBr have been investigated in a beatable tubular reactor coupled to a photoionization mass spectrometer. The reactions were studied by a time-resolved technique under pseudo-first-order conditions, where the rate constants of R + HBr reactions were obtained by monitoring the decay of the radical as a function of time. The radical was photogenerated in situ in the flow reactor by pulsed 248 nm exciplex laser radiation. All six reactions were studied separately over a wide range of temperatures and, in these temperature ranges, the rate constants determined were fitted to an Arrhenius expression (error limits stated are 1σ + Students t values, units cm3 molecule-1 s-1): k(n-C3H7) = (1.6 ± 0.2) × 10-12 exp[+(5.4 ± 0.2) kJ mol-1/RT], k(isoC3H7) = (1.4 ± 0.2) × 10-12 exp[+(6.9 ± 0.2) kJ mol-1/RT], k(n-C4H9) = (1.3 ± 0.2) × 10-12 exp[+(6.4 ± 0.4) kJ mol-1/RT], k(isoC4H9) = (1.4 ± 0.2) × 10-12 exp[+(6.1 ± 0.2) kJ mol-1/RT], k(sec-C4H9) = (1.4 ± 0.3) × 10-12 exp[+(7.5 ± 0.3) kJ mol-1/RT] and k(tert-C4H9) = (1.2 ± 0.3) × 10-12 exp[+(8.3 ± 0.3) kJ mol-1/RT]. The kinetic information was combined with the kinetics of the Br + RH reactions to calculate the entropy and the heat of formation values for the radicals studied. The thermodynamic values were obtained at 298 K using a second-law procedure. The entropy values and enthalpies of formation are (entropy in J K-1 mol-1 and enthalpy in kJ mol-1): 284 ± 5, 100.8 ± 2.1 (n-C3H7); 281 ± 5, 86.6 ± 2.0 (isoC3H7); 329 ± 5, 80.9 ± 2.2 (n-C4H9); 316 ± 5, 72.7 ± 2.2 (isoC4H9); 330 ± 5, 66.7 ± 2.1 (sec-C4H9) and 315 ± 4, 51.8 ± 1.3 (tert-C4H9). The C-H bond strength of analogous saturated hydrocarbons derived from the enthalpy of reaction values are (in kJ mol-1): 423.3 ± 2.1 (primary C-H bond in propane), 409.1 ± 2.0 (secondary C-H bond in propane), 425.4 ± 2.1 (primary C-H bond in n-butane), 425.2 ± 2.1 (primary C-H bond in isobutane), 411.2 ± 2.0 (secondary C-H bond in n-butane) and 404.3 ± 1.3 (tertiary C-H bond in isobutane). The enthalpy of formation values are used in group additivity calculations to estimate Δf H298○ values of six pentyl and four hexyl free radical isomers.
Functionalization of saturated hydrocarbons by aprotic superacids 4. Ionic bromination of ethane and other alkanes and cycloalkanes with molecular bromine in the presence of systems based on polyhalomethanes and AlBr3 under mild conditions
Akhrem,Orlinkov,Afanas'eva,Vol'pin
, p. 1148 - 1153 (2007/10/03)
Aprotic organic superacids CBr4 · 2AlBr3, CBr4 · AlBr3, · CCl4 · 2AlBr3, CCl4 · 2AlBr3, and C6F5CF3 · 2AlBr3 efficiently catalyze the bromination of alkanes and cycloalkanes with Br2. Ethane is selectively brominated at 55-65 °C to give mostly 1,2-dibromoethane (stoichiometric reaction). Propane, butane, cyclopentane, cyclohexane, and methyl-cyclopentane react with Br2 at -40 to -20 °C with good selectivity affording monobromides in high yields (catalytic reactions).
Methods for the synthesis of L-leucine selectively labelled with carbon-13 or deuterium in either diastereotopic methyl group
Kelly,Kelly, Nicholas M.,Reid,Gordon Reid,Willis,Willis, Christine L.,Winton,Winton, Peter L.
, p. 8315 - 8318 (2007/10/02)
A versatile approach is described for the enantioselective synthesis of isotopically labelled L-leucine involving the preparation of 4-methylpentanoic acid labelled selectively with carbon-13 or deuterium in either the pro-R or pro-S methyl group followed by a reductive amination of the ketone catalysed by leucine dehydrogenase. This strategy is applied to the total synthesis of (2S,4R)-[5,5,5-D3]-leucine using CD3I as the source of deuterium.
Ionic Bromination of Ethane and Other Alkanes (Cycloalkanes) with Bromine Catalyzed by the Polyhalomethane*2AlBr3 Aprotic Organic Superacids under Mild Conditions
Akhrem, Irena S.,Orlinkov, Alexander V.,Afanas'eva, Lyudmila V.,Mysov, Evgenii I.,Vol'pin, Mark E.
, p. 9365 - 9368 (2007/10/02)
The polyhalomethane*2AlBr3 aprotic organic superacids were shown to effectively catalyze low-temperature ionic bromination of (cyclo)alkanes.Ethane readily reacts with Br2 at 55-65 deg C, affording mainly 1,2-dibromoethane.Propane, butane, and C5-C6 cycloalkanes react at -40 - -20 deg C, resulting in monobromides with high yields and good selectivity.
SYNTHESIS OF SOME 2'-C-ALKYL DERIVATIVES OF 9-(2-PHOSPHONOMETHOXYETHYL)ADENINE AND RELATED COMPOUNDS
Cvorakova, Hana,Holy, Antonin,Rosenberg, Ivan
, p. 2069 - 2094 (2007/10/02)
To study the effect of β-substitution in 2'-alkyl derivatives of 9-(2-phosphonomethoxyethyl)adenine (Ia) on the antiviral activity or group specificity, these derivatives were synthesized. 9-(2-Hydroxyalkyl)adenines VIII were prepared by alkylation of adenine with suitably substituted oxiranes XIII or 2-hydroxyalkyl p-toluenesulfonates IV and VI.After protection of the adenine amino group by benzylation (compounds IX) or amidine formation (compounds X), the intermediates were alkylated with bis(2-propyl) p-toluenesulfonyloxymethanephosphonate (XI) in the presence of sodium hydride.After deprotection, the obtained phosphonate diesters XII were converted into phosphoniuc acids I by transsilylation and hydrolysis.This synthetic scheme was used for the preparation of ethyl (Ie), propyl (If), 2-propyl (Ig), 2-methylpropyl (Ih), cyclopropyl (Ii), cyclohexyl (Ij), benzyl (Ik) and phenyl (Il) derivatives.The 2'-trifluoromethyl derivative XXIIa was prepared analogously from 9-(2-hydroxy-3,3,3-trifluoropropyl)adenine (XXa), obtained by alkylation of adenine sodium salt with 2-hydroxy-3,3,3-trifluoropropyl bromide. 2,6-Diaminopurine derivative XXIIb was obtained analogously. 2'-Trimethylsilyl derivative XIXa was obtained by alkylation of adenine with 2-phosphonylmethoxy-3-(4-toluenesulfonyloxy)propyltrimethylsilane (XVII) followed by transsilylation and hydrolysis of diester XVIIIa. 9-(3-Phosphonomethoxybutyl)adenine (XXVIII) and 9-(2-methyl-2-phosphonomethoxypropyl)adenine (XXXV) were prepared from the corresponding hydroxy derivatives XXVIb and XXXII, respectively, by the same reaction pathway as derivatives I.
