7779-75-1

Usage

Uses

Used in Pharmaceutical Industry:
Isobutyl acetoacetate is used as an intermediate for the production of pharmaceuticals, such as Nisoldipine, a calcium channel blocker used to treat hypertension and angina.
Used in Chemical Synthesis:
Isobutyl acetoacetate is a building block that has been used as a reactant in the preparation of β-annulated 1,4-dihydropyridine derivatives, which act as TGFβ signaling inhibitors. These inhibitors have potential applications in the treatment of various diseases, including cancer and fibrosis.

Preparation

From isobutyl acetate by heating in the presence of sodium isobutylate.

InChI:InChI=1/C8H14O3/c1-6(2)5-11-8(10)4-7(3)9/h6H,4-5H2,1-3H3

Upstream product

• 674-82-8 4-methyleneoxetan-2-one 
• 78-83-1 2-methyl-propan-1-ol 
• 110-19-0 2-methylpropyl acetate 
• 13259-29-5 sodium isobutoxide 
• 123-86-4 acetic acid butyl ester 
• 141-97-9 ethyl acetoacetate 
• 2343-88-6 Acetoacetylfluorid 
• 105-45-3 acetoacetic acid methyl ester 
• 5394-63-8 2,2,6-trimethyl-4H-1,3-dioxin-4-one 
• 72324-39-1 5-acetyl-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 625-44-5 isobutyl methyl ether 
• 85920-63-4 5-(1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 57654-60-1 Bis-isobutyloxycarbonylmethyl-quecksilber 
• 75-36-5 acetyl chloride 

Downstream Products

• 52937-90-3 2-methyl-1-propyl 3-amino-2-butenoate 
• 106064-33-9 isobutyl 5-(benzyloxy)-3-oxopentanoate 
• 89080-63-7 2-(3-nitrobenzylidene)-acetoacetic acid isobutylester 
• 110544-72-4 4-(2-Difluoromethoxy-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diisobutyl ester 
• 111556-88-8 isobutyl methyl 2,6-dimethyl-4-<2-(trifluoromethyl)phenyl>-1,4-dihydropyridine-3,5-dicarboxylate 
• 111556-89-9 isobutyl methyl 2,6-dimethyl-4-<3-(trifluoromethyl)phenyl>-1,4-dihydropyridine-3,5-dicarboxylate 
• 591-60-6 butyl acetoacetate 
• 147597-19-1 2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-(2-cyano-ethyl) ester 5-isobutyl ester 
• 50639-30-0 isobutyl 2-diazoacetate 
• 27944-79-2 2,4-dimethylpentanal 
• 110-19-0 2-methylpropyl acetate 
• 67-64-1 acetone 
• 115-11-7 isobutene 
• 106064-44-2 isobutyl (3S)-5-benzyloxy-3-hydroxypentanoate 

Relevant academic research and scientific papers

N, N’-dimethyl formamide (DMF) mediated Vilsmeier–Haack adducts with 1,3,5-triazine compounds as efficient catalysts for the transesterification of β-ketoesters

N, N’-dimethyl formamide (DMF) mediated Vilsmeier–Haack (VH) adducts with 1,3,5-triazine compunds such as trichloroisocyanuric acid (TCCA) and trichlorotriazine (TCTA) were prepared by replacing classical oxy chlorides POCl3, and SOCl2, which were explored as efficient catalysts for the transesterification of β-ketoesters. The prepared (TCCA/DMF) and (TCTA/DMF) adducts improved greenery of the classical Vilsmeier–Haack reagents (POCl3/DMF), and (SOCl2/DMF), and demonstrated their better efficient catalytic ativity. Reaction times were in the range: 3.5 to 6.5 hr (SOCl2/DMF); 2.8–5.2 hr (POCl3/DMF); 2.5–5.2 hr (TCCA/DMF) and 2.5–5.0 hr (TCTA/DMF) catalytic systems. Ultrasonically (US) assisted protocols with these reagents further reduced the reaction times (two to three times), while microwave assisted (MW) protocols with these reagents were much more effective. The reactions could be completed in only few seconds (less than a minute) in MWassisted protocols as compared to US assited reactions, followed by good product yields.

Design, synthesis, and bioactivity of dihydropyrimidine derivatives as kinesin spindle protein inhibitors

A series of twenty-one 3,4-dihydropyrimidine derivatives bearing the heterocyclic 1,3-benzodioxole at position 4 in addition to different substituents at positions 2, 3 and 5 were designed and synthesized as monastrol analogs. The novel synthesized compounds were screened for their cytotoxic activity towards 60 cancer cell lines according to NCI (USA) protocol. Compounds 10b and 15 showed the best antitumor activity against most cell lines. Compound 15 was subsequently tested in 5-doses mode and displayed high selectivity towards CNS, prostate and leukemia subpanel with selectivity ratios of 22.30, 15.38 and 12.56, respectively at GI50 level. The IC50 of compounds 9d, 10b, 12, 15 and 16 against kinesin enzyme were 3.86 ± 0.12, 10.70 ± 0.35, 3.95 ± 0.12, 4.36 ± 0.14, and 14.07 ± 0.45 μM respectively, while the prototype compound, monastrol, reported IC50 value of 20 ± 0.42 μM. The safest compound among test compounds against normal cell line (HEK 293) is 10b with IC50 value of 62.02 ± 2.42 μM/ml in comparison to doxorubicin (IC50 = 11.34 ± 0.44 μM/ml). Cell cycle analysis of SNB-75 cells treated with compound 15 showed cell cycle arrest at G2/M phase. Further, the assay of levels of active caspase-3 and caspase-9 was investigated. Moreover, Molecular docking of compounds, 9d, 10b, 12, 15, 16, monastrol and mon-97 was performed to study the interaction between inhibitors and the kinesin spindle protein allosteric binding site.

A synthetic method of an m-nisoldipine medicine intermediate isobutyl acetoacetate

A synthetic method of an m-nisoldipine medicine intermediate isobutyl acetoacetate is disclosed. The method includes adding 10.6 mol of methyl iso-butyl ether and 3-3.2 mol of methylamine into a reactor provided with a stirrer, a thermometer, a reflux condenser and a dropping funnel, controlling the stirring speed to be 160-190 rpm, raising the temperature of the solution to 85-90 DEG C, adding dropwise 10.6-10.8 mol of diketene (2) while maintaining the reaction temperature to be 85-88 DEG C with the addition time being controlled to be 4-5 h, refluxing for 4 h after the addition is finished with the reaction solution being brown, cooling the solution until the temperature of the solution is 35-40 DEG C, washing with a salt solution, dehydrating with a dehydrating agent, performing vacuum distillation, and collecting a distillate at 109-115 DEG C to obtain the isobutyl acetoacetate (1). The mass percentage of the methylamine is 65-70%.

Prussian blue as an efficient catalyst for rate accelerations in the transesterification of β-ketoesters

Prussian blue triggered transesterification of ethylacetoacetate with various alcohols underwent efficiently. The reaction is mild, eco-friendly, and selective with good yields. The proposed reaction pathway depicts the formation of an intermediate by the interaction of β-ketoesters with catalytic site of the Prussian blue, followed by nucleophilic attack of the alcohol at the electrophilic center followed by successive elimination of the proton to give the product. Observed longer reaction times under conventional conditions reduced amazingly under sonication and microwave irradiation followed enhanced yield of products.

General and efficient transesterification of β-keto esters with various alcohols using Et3N as a br?nsted base additive

Transesterification of β-keto esters with a wide variety of allyl, benzyl, propargyl, and alkyl alcohols using, for the first time, commercially available and inexpensive Et3N as a Br?nsted base additive, is efficiently performed in toluene at reflux. The corresponding esters are exclusively obtained in 57-98% yields with no trace amounts of γ,δ-ketones, usually expected from the decarboxylative Carroll rearrangement.

Manganese(II) salts as efficient catalysts for chemo selective transesterification of β-keto esters under non-conventional conditions

Transesterification of β-ketoesters with various alcohols has been studied under conventional and non-conventional conditions using desktop chemicals such as Mn(II) salts as catalysts. These methods offered transesterification of β-ketoesters in good yields with dramatic rate accelerations and reduced reaction times. The developed protocols under nonconventional methods such as sonication and microwave irradiation are highly promising compared with the existing procedures.

An efficient synthesis of β-ketoesters via transesterification and its application in Biginelli reaction under solvent-free, catalyst-free conditions

A simple and efficient transesterification process for the synthesis of β-ketoester derivatives has been achieved by the reaction of methyl β-ketoester with higher alcohols at 110 C under solvent-free, catalyst-free conditions and its application in synthesis of 3,4-dihydropyrimidin-2(1H)-ones C-5 ester derivatives via Biginelli reaction has been described.

AgOTf-catalyzed transesterification of β-keto esters

AgOTf proved to be an effective catalyst for the transesterification of β-keto esters with primary, secondary and tertiary alcohols. The products were obtained in high yield within a reasonable reaction time period. The kinetics of the transesterification reaction were also studied and the reaction was found to follow second-order kinetics. Copyright

Design and synthesis of new 1,4-dihydropyridines containing 4(5)-chloro-5(4)-imidazolyl substituent as a novel calcium channel blocker

New analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 has been replaced by 4(5)-chloro-5(4)-imidazolyl substituent and which are able to interact with the receptor by hydrogen binding were designed, synthesized, and evaluated as calcium channel antagonists. The designed dihydropyridines were synthesized using the Hantzsch condensation and evaluated as calcium channel antagonists using the high K+ contraction of guineapig ileal longitudinal smooth muscle. A docking study was performed using the AutoDock4 program, and QSAR equations were obtained using multilinear regression. Our computational studies indicated that the oxygen of the ester (O10) and the N3′ of the imidazole ring form a hydrogen bonding interaction with the NH of HIS 363 and NH of LYS354, respectively, and that the sum of the BEHp5 and RDF075p are the most significant descriptors. The results of calcium channel antagonist evaluation demonstrated that increasing the chain length in C3 and C5 ester substituents increased activity. The most potent compound was the bis-phenylpropyl ester (5l) derivative, in that it was more active than the reference drug nifedipine and that the bis-phenylethyl ester (5k) derivative had comparable activity with nifedipine. The present research revealed that the 4(5)-chloro-5(4)-imidazolyl moiety is a bioisoster of o-nitrophenyl in nifedipine and provided novel dihydropyridines with more activity as calcium channel antagonists.

Efficient trans-acetoacylation mediated by ytterbium(III) triflate as a catalyst under solvent-free condition

A simple and efficient trans-acetoacylation method for the synthesis of β-keto ester derivatives has been described using ytterbium(III) triflate as a new catalyst under solvent-free condition. This method was found to be efficient and convenient for the synthesis of a wide variety of β-keto ester derivatives.