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Chemical Structure| 13395-36-3 Chemical Structure| 13395-36-3
Chemical Structure| 13395-36-3

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Ethyl 5,5-dimethyl-2,4-dioxohexanoate

CAS No.: 13395-36-3

4.5 *For Research Use Only !

Cat. No.: A158792 Purity: 98%

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Product Details of [ 13395-36-3 ]

CAS No. :13395-36-3
Formula : C10H16O4
M.W : 200.23
SMILES Code : CCOC(=O)C(=O)CC(=O)C(C)(C)C
MDL No. :MFCD00052319
InChI Key :NIMKIMUBJFWPTD-UHFFFAOYSA-N
Pubchem ID :83403

Safety of [ 13395-36-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Calculated chemistry of [ 13395-36-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.7
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 51.61
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

60.44 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.78
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.62
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.12
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.64
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.37

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.71
Solubility 3.94 mg/ml ; 0.0197 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.5
Solubility 0.631 mg/ml ; 0.00315 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.88
Solubility 2.65 mg/ml ; 0.0132 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.37 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

2.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.06

Application In Synthesis [ 13395-36-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 13395-36-3 ]

[ 13395-36-3 ] Synthesis Path-Downstream   1~25

  • 2
  • [ 626-34-6 ]
  • [ 13395-36-3 ]
  • 6-<i>tert</i>-butyl-2-methyl-pyridine-3,4-dicarboxylic acid diethyl ester [ No CAS ]
  • 3
  • [ 626-34-6 ]
  • [ 13395-36-3 ]
  • 3-(1-amino-ethylidene)-2-(3,3-dimethyl-2-oxo-butyl)-2-hydroxy-succinic acid diethyl ester [ No CAS ]
  • 4
  • [ 75-87-6 ]
  • [ 13395-36-3 ]
  • 4-pivaloyl-5-trichloromethyl-dihydro-furan-2,3-dione [ No CAS ]
  • 5
  • [ 13395-36-3 ]
  • [ 107-91-5 ]
  • [ 100616-09-9 ]
  • 6
  • [ 13395-36-3 ]
  • [ 91252-54-9 ]
YieldReaction ConditionsOperation in experiment
65% With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; for 16h;Reflux; The title compound is prepared by those skilled in the art according to a literature procedure (Lepage et al, Eur. J. Med. Chem., 1992, 27, 6, 581-93).To a solution of sodium hydrogen carbonate (2.10 g, 25 mmol) and hydroxylamine hydrochloride (1.73 g, 25 mmol) in ethanol (25 mL) is added ethyl trimethyl acetopyruvate (5.00 g, 25 mmol). The mixture is heated at reflux for 16 h. After this time the sodium chloride is removed by filtration and the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on silica eluting with 8/2 cyclohexane/ethyl acetate to provide the title compound as a yellow oil (3.2 g, 65%), m/z 198 [M+H+]. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.38 (9 H, s), 1.42 (3 H, t, /=7.15 Hz), 4.44 (2 H, q, /=7.15 Hz), 6.38 (1 H, s).
65% With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; for 16h;Reflux; Step 1: Synthesis of 5-tert-butyl-isoxazole-3-carboxylic acid ethyl ester The title compound is prepared by those skilled in the art according to a literature procedure (Lepage et al, Eur. J. Med. Chem., 1992, 27, 6, 581-93). To a solution of sodium hydrogen carbonate (2.10 g, 25 mmol) and hydroxylamine hydrochloride (1.73 g, 25 mmol) in ethanol (25 mL) is added ethyl trimethyl acetopyruvate (5.00 g, 25 mmol). The mixture is heated at reflux for 16 h. After this time the sodium chloride is removed by filtration and the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on silica eluting with 8/2 cyclohexane/ethyl acetate to provide the title compound as a yellow oil (3.2 g, 65%), m/z 198 [M+H+]. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.3 8 (9 H, s), 1.42 (3 H, t, J=7.15 Hz), 4.44 (2 H, q, J=7.15 Hz), 6.38 (1 H, s).
  • 8
  • [ 75-97-8 ]
  • [ 95-92-1 ]
  • [ 13395-36-3 ]
YieldReaction ConditionsOperation in experiment
93.3% To a solution of sodium ethoxide (740mmol of sodium in 45OmL ethanol), a mixture of methyl tert-bxAy ketone (740mmol) and diethyl oxalate (820mmol) are added dropwise at room temperature and stirred for Ih at 78C. On complete reaction, the mixture is allowed to cool to room temperature and it is poured onto cold aqueous hydrochloric acid (5M, 800 mL). Following extraction with methyl tert-butyl ether (300 mL x 3), the combined organic phases are washed with saturated aqueous sodium chloride (500 mL) and dried over anhydrous sodium sulfate. After filtration, removal of the solvent under reduced pressure affords the product as a red liquid. Compound wt: 14Og, Yield: 93.3%.[00292] MS (ES+): 199 (M+l). NMR (1H, CDCl3): 6.5 (IH, s, CH); 4.3 (2H, q, OCH2); 1.35 (3H, t, CH3); 1.15 (9H, s, 3xCH3).
74.6% With sodium; In ethanol; at 0 - 20℃; General procedure: A mixture of ketone 15(0.087 mol), diethyl oxalate 16(0.087mol),thinly sliced sodium (0.047mol) in ethanol (55 mL) was first stirred at 0 and then stirred over night at room temperature. After complication, the mixture was acidified(pH3.0,with 20% H2SO4), filtered and extracted with dichloromethane.The organic phase was dried and concentrated under vacuum to obtainan yellow or orange liquid 17a-e. The 1,3-diketone 17a-e(0.025mol) was dissolved in methanol (10mL),then added dropwise to a cooled solution(0C) of hydrazinobenzene(0.025 mol) in methanol (30mL). The reaction was stirred for an hour at room temperature, refluxed for 2h,and the solvent was evaporated under reduced pressure. The residual liguid was purified by column chromatography (a5% gradient of ethyl acetate in hexanes over a column of silica gel) to afford immediate 18a-e.To obtain the acid 19a-e, a solution of 18a-e(0.007 mol) was saponified through adding7ml 6 mol/L NaOH and stirring at 80Cfor 2 h.The mixture was acidified (pH1-2) with concentrated hydrochloric acid and filtered to afford 19a-e.To a solution of 19a-e(0.010mol) in 15ml DMF, NCS (0.010mol) was added.The reaction mixture was heated at 90C for 1hand then added to ice water(50ml), and filtered t oobtain 4-chlorosubstituted carboxylic acids 20a-e. The amide derivatives 21-38 were prepared through the acyl chlorides derived from 19 a-e or 20a-e. A solution of 19a-e or 20a-e(0.004mol) in thionyl chloride(10mL) was refluxed for 5 h and then concentrated under vacuum. The crude acylchloride was added dropwise to a cooled solution(0C) of substituted aniline (0.004mol) and TEA (0.008mol)in dichloromethane (10mL). The mixture was stirred overnight at room temperature, and then purified on a column of silica using a gradient of ethylacetate in hexanes to afford the pure products.The yields of imtermediate 17a-e, 18a-e, 19a-e and 20a-e are listed intable 1S.
74.6% With sodium; In ethanol; at 0 - 20℃; Pinacolone 1 (0.087 mol) and diethyl oxalate 2 (0.087 mol) were added dropwise to a solution of ethanol (55 mL) containing thinly sliced sodium (0.047 mol) at 0 C. The mixture was stirred overnight at room temperature. Next morning, the mixture was acidified (pH 3.0, with 20% H2SO4) and filtered to remove the formed solid. The filtrate was extracted with dichloromethane, dried, and concentrated under vacuum to yield an orange red viscous liquid 3 (12.98 g; 74.6% y). A solution of the 1,3-diketone 3 (0.025 mol) in methanol (10 mL) was added dropwise to a cooled solution (0 C) of hydrazinobenzene (0.025 mol) in methanol (30 mL). The mixture was warmed to room temperature by stirring for an hour and then refluxed for 2 h. The resulting cooled mixture was concentrated under vacumm and the pyrazole ester 4 was obtained after purification by column chromatography (a 5% gradient of ethyl acetate in hexanes over a column of silica gel). To saponify the ester, a solution of 4 (0.007 mol) was combined with an aliquot of 6 mol/L NaOH (aq) (7 mL) and the mixture was stirred at 80 C. Ice water (50 mL) was added at the end of 2 h and the mixture was acidified (pH 1-2) with concentrated HCl. The formed solid was collected by filtration and the filter-cake was dried. The carboxylic acid was purified by recrystallization (methanol:water, 1:1) to afford 5 (3.57 g; 83.2% yield). The amide derivatives 6a-p were prepared through the acylchlorides derived from 5. A solution of 5 (0.004 mol) in thionyl chloride (10 mL) was refluxed for 5 h [11] and then concentrated under vacuum. The formed crude acyl chloride was added dropwise to a cooled solution (0 C) of substituted aniline (0.004 mol) and TEA (0.008 mol) in dichloromethane (10 mL). The resulting mixture was stirred overnight at room temperature to produce the crude product, which was purified on a column of silica using a gradient of ethyl acetate in hexanes to afford the pure products 6a-p.
70% A mixture of tert-butyl ketone (499 mmol) and diethyl oxalate (548 mmol) in ethanol(550 mL) is added slowly to the solution of sodium (499 mmol) in ethanol (250 mL) at room temperature. After addition, the reaction mixture is heated to 600C for 2 h. On complete reaction, the ethanol is removed under reduced pressure and aqueous hydrochloric acid (2M, 200 mL) is added to the residue. The aqueous phase is extracted with ethyl acetate (500 mL x 3), washed with water (300 mL), saturated aqueous sodium chloride (300 mL) and it is then dried over anhydrous sodium sulfate. The solvent is then removed under reduced pressure to afford 5,5-dimethyl-2,4-dioxo-hexanoic acid ethyl ester as orange colored liquid (72.5g, 70%).[0205] 1H NMR (400 MHz, CDCl3) delta: 1.20 (s, 9H), 1.35 (t, 3H), 4.34 (q, 2H), 6.53 (s, IH), 14.75(bs, IH). Mass (m/z): 201 (M+H).
With sodium hydride; In toluene; mineral oil; at 50℃; for 1.5h;Reflux; General procedure: To a stirred solution of appropriate methyl ketone (0.1 mol) in dry toluene (200 mL)was added a suspension of NaH in mineral oil (60%; 0.2 mol) in portions and the mixture was warmed to50 C. At this temperature a solution of diethyl oxalate (0.15 mol) in dry toluene (60 mL) was addeddropwise under stirring. The reaction mixture was refluxed for 1.5 h. Upon cooling to room temperatureacetic acid (0.25 mol) was added dropwise. The reaction mixture was washed with water (200 mL), organicphase was dried over MgSO4 and evaporated to dryness. The obtained crude diketone was dissolved inethanol (250 mL), hydrazine dihydrochloride (0.11 mol) was added and the mixture was refluxed for 3 h.After evaporation of solvent the residue was treated with water (200 mL) and kept under ice-cooling for 1 h.Crystals were filtered off and dried in air to afford the corresponding pyrazole. In some cases thus obtainedsubstance was purified by recrystallization from aqueous ethanol.
With sodium ethanolate; at 0 - 78℃; for 1h; To a solution of sodium ethoxide (740 mmol of sodium in 450 mL ethanol), a mixture of methyl tert-butyl ketone (740 mmol) and diethyl oxalate (820 mmol) were added dropwise at room temperature and stirred for 1 h at 78 C. On completion of the reaction, the mixture was allowed to cool to room temperature and poured onto cold aqueous hydrochloric acid (5M, 800 mL). Following extraction with methyl tert-butyl ether (300 mL*3), the combined organic phases were washed with saturated aqueous sodium chloride (500 mL) and dried over anhydrous sodium sulfate. After filtration, removal of the solvent under reduced pressure afforded the product as a red liquid. Compound wt: 140 g, Yield: 93.3%. MS (ES+): 199 (M+1). NMR (1H, CDCl3): 6.5 (1H, s, CH); 4.3 (2H, q, OCH2); 1.35 (3H, t, CH3); 1.15 (9H, s, 3*CH3).

  • 9
  • [ 54153-51-4 ]
  • [ 13395-36-3 ]
  • ethyl 8-cyano-2-ter.butyl-7-phenylpyrrolo<1,2-a>pyrimidin-2-carboxylate [ No CAS ]
  • ethyl 8-cyano-2-ter.butyl-7-phenylpyrrolo<1,2-a>pyrimidin-4-carboxylate [ No CAS ]
  • 10
  • [ 13395-36-3 ]
  • [ 75-97-8 ]
  • 11
  • [ 13395-36-3 ]
  • [ 17094-34-7 ]
  • [ 201230-82-2 ]
  • 12
  • [ 13395-36-3 ]
  • [ 60-34-4 ]
  • [ 133261-10-6 ]
  • [ 194289-30-0 ]
  • 13
  • [ 13395-36-3 ]
  • ethyl 2-hydroxy-4-oxo-5,5-dimethylhexanoate [ No CAS ]
  • 14
  • [ 13395-36-3 ]
  • ethyl (S)-2-hydroxy-4-oxo-5,5-dimethylhexanoate [ No CAS ]
  • ethyl (R)-2-hydroxy-4-oxo-5,5-dimethylhexanoate [ No CAS ]
  • 15
  • [ 13395-36-3 ]
  • ethyl (S)-2-hydroxy-4-oxo-5,5-dimethylhexanoate [ No CAS ]
  • ethyl (R)-2-hydroxy-4-oxo-5,5-dimethylhexanoate [ No CAS ]
  • syn-3-hydroxy-5-tertiobutyltetrahydrofuran-2-one [ No CAS ]
  • anti-(+)-3-hydroxy-5-tertiobutyltetrahydrofuran-2-one [ No CAS ]
  • 16
  • [ 13395-36-3 ]
  • ethyl (S)-2-hydroxy-4-oxo-5,5-dimethylhexanoate [ No CAS ]
  • syn-3-hydroxy-5-tertiobutyltetrahydrofuran-2-one [ No CAS ]
  • anti-(-)-3-hydroxy-5-tertiobutyltetrahydrofuran-2-one [ No CAS ]
  • 17
  • [ 13395-36-3 ]
  • NaOH-solution , aqueous [ No CAS ]
  • [ 64165-15-7 ]
  • 18
  • [ 13395-36-3 ]
  • natrium carbonat, aqueous [ No CAS ]
  • [ 64165-15-7 ]
  • 19
  • [ 13395-36-3 ]
  • diluted NaOH-solution [ No CAS ]
  • [ 75-97-8 ]
  • [ 144-62-7 ]
  • 20
  • [ 13395-36-3 ]
  • natrium carbonate [ No CAS ]
  • [ 75-97-8 ]
  • [ 144-62-7 ]
  • 22
  • [ 593-56-6 ]
  • [ 13395-36-3 ]
  • [ 1001420-17-2 ]
YieldReaction ConditionsOperation in experiment
75% In ethanol; at 20℃; for 15h;Molecular sieve; To a solution of <strong>[13395-36-3]ethyl trimethylacetopyruvate</strong> (205 mg, 1.02 mmol) in dry EtOH (1 mL) was added O-methylhydroxylamine hydrochloride (90 mg, 1.07 mmol) and 3A mol. sieves. The reaction was stirred at RT for 15 h, then was filtered and washed with EtOH. The filtrated was concentrated in vacuo, and the residue was partitioned between Et2O and sat. aqueous NaHCO3. The Et2O layer was washed with water and brine, dried (MgSO4) and concentrated in vacuo to give Part A compound (176 mg, 75%) as a red-orange oil.
  • 23
  • [ 1012879-55-8 ]
  • [ 13395-36-3 ]
  • [ 1020173-68-5 ]
YieldReaction ConditionsOperation in experiment
40 g With hydrogenchloride; In ethanol; at 80℃; A solution of N-benzhydrylidene-N'-quinolin-6-yl-hydrazine (32 g, 0.099 mol) in EtOH (500 mL) was treated with cone. HC1 (80 ml, 0.96 mmol). After stirring for 10 min, <strong>[13395-36-3]5,5-dimethyl-2,4-dioxo-hexanoic acid ethyl ester</strong> (26 g, 0.15 mol) was added, and the mixture was heated to 80C overnight. The reaction was concentrated in vacuo to give a residue which was washed with Et20 to afford ethyl 5- tert-butyl-l-(quinolin-6-yl)-lH-pyrazole-3-carboxylate hydrochloride (40 g, 0.1 1 mol, 1 12 % yield). MS (ESI) m/z: 324.1 (M+H+).
  • 24
  • [ 13395-36-3 ]
  • [ 83405-70-3 ]
YieldReaction ConditionsOperation in experiment
70% With hydrazine; In ethanol; at 20℃; Hydrazine hydrate (446 mmol) is added dropwise to solution of 5,5-dimethyl-2,4-dioxo- hexanoic acid ethyl ester (360 mmol) in ethanol at room temperature. After addition, the reaction mixture is stirred overnight at room temperature. On completion, the solvent is removed under reduced pressure and the residue obtained is diluted with water (250 mL) and extracted with dichloromethane (250 mL x are3). The combined organic phases are washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate. The solvent is removed under reduced pressure to afford 5-tert-butyl-2H- pyrazole-3-carboxylic acid ethyl ester as a white crystalline solid (70%).[0207] 1H NMR (400 MHz, DMSO-d6) delta: 13.21 (bs, IH), 6.45 (s, IH), 4.23 (q, 2H), 1.27 (s,9H,)1.25 (t, 3H). Mass (m/z): 197 (M+H).
11 g With hydrazine dihydrochloride; In ethanol; for 3h;Reflux; General procedure: To a stirred solution of appropriate methyl ketone (0.1 mol) in dry toluene (200 mL)was added a suspension of NaH in mineral oil (60%; 0.2 mol) in portions and the mixture was warmed to50 C. At this temperature a solution of diethyl oxalate (0.15 mol) in dry toluene (60 mL) was addeddropwise under stirring. The reaction mixture was refluxed for 1.5 h. Upon cooling to room temperatureacetic acid (0.25 mol) was added dropwise. The reaction mixture was washed with water (200 mL), organicphase was dried over MgSO4 and evaporated to dryness. The obtained crude diketone was dissolved inethanol (250 mL), hydrazine dihydrochloride (0.11 mol) was added and the mixture was refluxed for 3 h.After evaporation of solvent the residue was treated with water (200 mL) and kept under ice-cooling for 1 h.Crystals were filtered off and dried in air to afford the corresponding pyrazole. In some cases thus obtainedsubstance was purified by recrystallization from aqueous ethanol.
  • 25
  • [ 13395-36-3 ]
  • 5-<i>tert</i>-butyl-1(2)<i>H</i>-pyrazole-3-carboxylic acid [ No CAS ]
 

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