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Chemical Structure| 6914-71-2 Chemical Structure| 6914-71-2
Chemical Structure| 6914-71-2

1,1-Cyclopropanedicarboxylic acid dimethyl ester

CAS No.: 6914-71-2

4.5 *For Research Use Only !

Cat. No.: A500494 Purity: 95%

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Product Details of [ 6914-71-2 ]

CAS No. :6914-71-2
Formula : C7H10O4
M.W : 158.15
SMILES Code : COC(=O)C1(CC1)C(=O)OC
MDL No. :MFCD00192079
InChI Key :PWLLZZMFFZUSOG-UHFFFAOYSA-N
Pubchem ID :2769539

Safety of [ 6914-71-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335-H412
Precautionary Statements:P261-P273-P305+P351+P338

Calculated chemistry of [ 6914-71-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 0.71
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 35.96
TPSA ?

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

52.6 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.16
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

0.48
Log Po/w (WLOGP)?

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

0.05
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.

0.21
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

0.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.74

Water Solubility

Log S (ESOL):?

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

-0.86
Solubility 21.9 mg/ml ; 0.138 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.

-1.15
Solubility 11.1 mg/ml ; 0.0702 mol/l
Class?

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

Very 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

-0.84
Solubility 22.9 mg/ml ; 0.145 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

No
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.

-6.92 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

1.0
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)

1.56

Application In Synthesis [ 6914-71-2 ]

* 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 [ 6914-71-2 ]

[ 6914-71-2 ] Synthesis Path-Downstream   1~26

  • 4
  • C8H13LiO4Se [ No CAS ]
  • [ 6914-71-2 ]
  • [ 127628-39-1 ]
  • 5
  • C8H13NaO4Se [ No CAS ]
  • [ 6914-71-2 ]
  • [ 127628-38-0 ]
  • [ 127628-39-1 ]
  • 6
  • methyl 2-carbomethoxy-2-potassio-4-methylseleno butyrate [ No CAS ]
  • [ 6914-71-2 ]
  • [ 127628-38-0 ]
  • [ 127628-39-1 ]
  • 7
  • [ 107-06-2 ]
  • [ 108-59-8 ]
  • [ 6914-71-2 ]
YieldReaction ConditionsOperation in experiment
79.7% With tetrabutylammomium bromide; potassium carbonate; Comparative Example 2 Dimethyl 1,1-cyclolpropanedicarboxylate without polyethylene glycol/derivative addition 450.3 9 of 1,2-dichloroethane (4.55 mol) and 168 g of potassium carbonate (1.2 mol) were initially introduced and the reaction mixture was heated until the 1,2-dichloroethane refluxes. 99.1 g of dimethyl malonate (0.75 mol) and 1.25 g of tetrabutylammonium bromide (3.88 mmol) were then added at the boil. Water formed during the reaction was removed by azeotropic distillation with 1,2-dichloroethane throughout the reaction. After a reaction time of 5 hours, the reaction mixture was cooled and separated off from the reaction salt by filtration. By means of fractional distillation, 1,2-dichloroethane was obtained at a reduced pressure and dimethyl 1,1-cyclopropanedicarboxylate was obtained at up to 10 mbar (=100 Pa). The yield was 79.7percent.
  • 8
  • [ 106-93-4 ]
  • [ 108-59-8 ]
  • [ 75-21-8 ]
  • [ 6914-71-2 ]
  • [ 107-21-1 ]
  • 10
  • methylphenylvinylselenonium tetrafluoroborate [ No CAS ]
  • [ 108-59-8 ]
  • [ 6914-71-2 ]
  • 11
  • ethylphenylvinylselenonium tetrafluoroborate [ No CAS ]
  • [ 108-59-8 ]
  • [ 6914-71-2 ]
  • 12
  • [ 6914-71-2 ]
  • [ 37773-10-7 ]
  • [ 74-88-4 ]
  • [ 113020-26-1 ]
  • 13
  • [ 700-58-3 ]
  • [ 6914-71-2 ]
  • C16H22O4 [ No CAS ]
  • 14
  • [ 2550-26-7 ]
  • [ 6914-71-2 ]
  • 6-Methyl-2-oxo-6-phenethyl-tetrahydro-pyran-3-carboxylic acid methyl ester [ No CAS ]
  • 16
  • [ 6914-71-2 ]
  • [ 108-94-1 ]
  • 2-Oxo-1-oxa-spiro[5.5]undecane-3-carboxylic acid methyl ester [ No CAS ]
  • 17
  • [ 6914-71-2 ]
  • [ 830-13-7 ]
  • 2-Oxo-1-oxa-spiro[5.11]heptadecane-3-carboxylic acid methyl ester [ No CAS ]
  • 18
  • [ 6914-71-2 ]
  • [ 98-86-2 ]
  • 6-Methyl-2-oxo-6-phenyl-tetrahydro-pyran-3-carboxylic acid methyl ester [ No CAS ]
  • 19
  • [ 6914-71-2 ]
  • [ 67-64-1 ]
  • 6,6-Dimethyl-2-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester [ No CAS ]
  • 20
  • [ 6914-71-2 ]
  • [ 96-22-0 ]
  • 6,6-Diethyl-2-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester [ No CAS ]
  • 21
  • [ 6914-71-2 ]
  • [ 2043-61-0 ]
  • 6-Cyclohexyl-2-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester [ No CAS ]
  • 22
  • [ 6914-71-2 ]
  • [ 762-72-1 ]
  • [ 93185-10-5 ]
  • 23
  • [ 6914-71-2 ]
  • [ 102-04-5 ]
  • 5,5-dibenzyl-2-methoxycarbonyl-5-pentanolide [ No CAS ]
  • 24
  • C14H18 [ No CAS ]
  • [ 6914-71-2 ]
  • dimethyl spiro<2,4>heptane-4,4-dicarboxylate [ No CAS ]
  • 25
  • [ 105-34-0 ]
  • [ 108-59-8 ]
  • [ 6914-71-2 ]
  • [ 38806-09-6 ]
YieldReaction ConditionsOperation in experiment
Example 1 Dimethyl cyclopropane-1,1-dicarboxylate 2.1 mol of DMM, 6.6 mol of EDC, 2.4 mol of potash having fractions of 87percent by weight with particle sizes of <0.1 mm and fractions of 78percent by weight with particle sizes of <0.05 mm and 6.5 mol of DMF are taken in a reaction vessel having a stirrer and distillation attachment with condenser and phase separation vessel. The mixture is heated to 110° C. with stirring, water of reaction distilling off azeotropically with EDC. The water of reaction is taken off as the upper phase, and the EDC, the lower phase, is recycled to the reaction. After 1.5 h, 65percent of the DMM has been converted. 0.008 mol of TBAB as a 50percent strength by weight aqueous solution is added in the course of 30 min. The evolution of carbon dioxide increases again. After a further hour, i.e. after 3 h from the beginning of the reaction, a DMM conversion of about 98percent is reached. The reaction is then complete; the reaction of the remaining DMM takes place in the subsequent working-up stage. Excess EDC is distilled off from the reaction mixture, initially at a temperature of from 110 to 120° C., the DMM conversion increasing to >99percent. Volatile fractions of high boilers and salt are then separated off using a rotary evaporator (160° C., 1 mbar). The distillate, predominantly DMF and the desired product dimethyl cyclopropane-1,1-dicarboxylate, is subjected to fractional distillation. The desired product is obtained in a purity of 99.3percent (GC analysis) and with a yield of about 83percent of theory, based on DMM used. The exit gas escaping from the reaction (predominantly CO2 and a small amount of H2O, vinyl chloride and EDC) is fed to an incineration unit for chlorinated hydrocarbons. The valuable substances EDC and DMF obtained in the working up of the reaction batch by distillation can be used for a further batch.
 

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Technical Information

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