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Chemical Structure| 30095-98-8 Chemical Structure| 30095-98-8

Structure of Methyl (2-nitrophenyl)acetate
CAS No.: 30095-98-8

Chemical Structure| 30095-98-8

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Product Details of [ 30095-98-8 ]

CAS No. :30095-98-8
Formula : C9H9NO4
M.W : 195.17
SMILES Code : O=C(OC)CC1=CC=CC=C1[N+]([O-])=O
MDL No. :MFCD00968465
InChI Key :SWMFAAPTSMVULA-UHFFFAOYSA-N
Pubchem ID :520464

Safety of [ 30095-98-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 30095-98-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 51.13
TPSA ?

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

72.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.79
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

1.91
Log Po/w (WLOGP)?

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

1.31
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.

0.89
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

-0.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.16

Water Solubility

Log S (ESOL):?

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

-2.31
Solubility 0.964 mg/ml ; 0.00494 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-3.05
Solubility 0.175 mg/ml ; 0.000896 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

-2.26
Solubility 1.07 mg/ml ; 0.00546 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

Yes
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.

-6.13 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)

1.95

Application In Synthesis of [ 30095-98-8 ]

* 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 [ 30095-98-8 ]

[ 30095-98-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 30095-98-8 ]
  • [ 35613-44-6 ]
YieldReaction ConditionsOperation in experiment
98% With palladium on activated charcoal; hydrogen; In toluene; at 5℃; under 760.051 Torr; Compound 2 (97.6 g, 0.5 mol),Pd/C (0.98g) and toluene (200mL) were placed in the reaction flask.Hydrogen was passed through a hydrogenation reaction at normal pressure of 5 C overnight.After the reaction,filter,Wash with a small amount of toluene,Combine the filtrate and the wash solution,Recovering toluene,Precipitating solids,Vacuum drying,The pale yellow liquid was Intermediate 3 (80.9 g, 98%).
97% With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; Preparation of methyl 2-(2-aminophenyl)acetate (Compound 6-1) [00231j A mixture of Compound 1-2 (9.75 g, 50 mmol), 10% palladiumlactivecarbon catalyst (dry, 530 mg, 5 mmol) in methanol (100 mL) was stirred under hydrogen atmosphere at room temperature for overnight. The reaction mixture was filtered to remove palladiumlactive carbon catalyst and the filtrate was concentrated to give Compound 6-1 (8.02 g, yield: 97%) as a pale yellow oil. MS (ES): mlz:166[M+H]. ?H NMR (400 MHz, DMSO-d6) oe: 6.94 (m, 2H), 6.64 (d, 1H, J 8.0 Hz),6.51 (m, 1H), 4.88 (s, 2H), 3.59 (s, 3H), 3.52 (s, 2H).
97% With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; under 760.051 Torr; Preparation of methyl 2-(2-aminophenyl)acetate (Compound 11-3)[00269j A mixture of methyl 2-(2-nitrophenyl)acetate (Compound 11-2, 9.75 g, 50 mmol), 10% palladiumlactive carbon catalyst (dry, 530 mg, 5 mmol) in methanol (100 mL) was stirred under H2 (1 atm.) at room temperature overnight. The reaction mixture was filtered to remove palladiumlactive carbon catalyst and the filtrate was concentrated to give the desired product methyl 2-(2-aminophenyl)acetate (Compound 11-3, 8.02 g, yield: 97%) as a pale yellow oil. MS (ESI): mlz: 166[M+H]. ?H NMR (400 MHz, DMSO-d6) oe: 6.94 (m, 2H), 6.64 (d, 1H, J= 8.0 Hz), 6.51 (m, 1H), 4.88 (s, 2H), 3.59 (s, 3H), 3.52 (s, 2H).
67% With hydrogen;palladium 10% on activated carbon; In ethyl acetate; at 20℃; for 2h; The 2-nitrophenyl acid methyl ester (1 g, 5.13 mmol) was dissolved in 20 mL of EA and 0.3 g of Pd/C 10% was suspended into the solution, the reaction mixture was under hydrogen atmosphere at room temperature. After 2h the reaction was completed by TLC analysis (DCM: EA 60; 40) the Pd/C 10% was removed by filtration and the solvent by reduced pressure; to yield a colorless oil 0.67 g (67%).
8.5 g (100%) palladium-carbon; In methanol; B. Methyl 2-aminophenylacetate. Methyl 2-nitrophenylacetate (10.1 g, 51.2 mmol) in 125 mL of methanol containing 221 mg of 10% Pd/C was placed on the Parr hydrogenator at 40 psi. After 5 h the mixture was filtered through celite and evaporated under reduced pressure to give a clear red oil. The solvent was evaporated under reduced pressure to give 8.5 g (100%) of methyl 2-aminophenylacetate as a clear red oil. TLC (silica, EtOAc/hexanes): Rf=0.24. 1H NMR (400MHz, CDCl3): 7.21 (m, 2H), 6.86 (m, 2H), 3.81 (s, 3H), 3.70 (s, 2H).
With hydrogen;platinum(IV) oxide; In methanol; under 2585.81 - 2844.39 Torr; for 25.5h; B. (2-Amino-phenyl) acetic acid methyl ester; The title A compound, (2-nitro-phenyl)-acetic acid methyl ester (5.0 g, 25.6 mmol) is dissolved in MeOH (125 mL) in a Parr Bottle. It is purged with nitrogen, then added Pt02 (185 mg), then placed on a Parr Shaker under 50 to 55 psi of hydrogen with shaking for 25.5 h. The reaction is opened and filtered through celite, and concentrated to yield (2-amino- phenyl) acetic acid methyl ester as an amber oil : [M+1] + = 166.
With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃;Inert atmosphere; Add Pd/C (10%, 800 mg) to a solution of methyl 2-(2-nitrophenyl)acetate (7.5 g, 38.5 mmol) in methanol (50 mL) under N2, then flush with H2, stir the reaction under atmosphere at room temperature overnight. Remove the hydrogen; filter off the solid, concentrate the filtrate under reduced pressure to obtain the crude product (4.8 g, 76.2%) which is used directly without further purification. MS: (M+l):166
With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃;Inert atmosphere; Add Pd/C (10%, 800 mg) to a solution of methyl 2-(2-nitrophenyl)acetate (7.5 g, 38.5 mmol) in methanol (50 mL) under N2, then flush with H2, stir the reaction under H2 atmosphere at room temperature overnight. Remove the hydrogen; filter off the solid, concentrate the filtrate under reduced pressure to obtain the crude product (4.8 g, 76.2%) which is used directly without further purification. MS: (M+1):166.

  • 3
  • [ 30095-98-8 ]
  • [ 35613-44-6 ]
  • [ 124-63-0 ]
  • methyl 2-(methylsulfonylamino)phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With magnesium sulfate; triethylamine;palladium; In toluene; To a solution of methyl 2-nitrophenylacetate, (6.04 kg) in toluene (100 l) is added anhydrous magnesium sulfate (2.00 kg) and then 5% palladium-on-charcoal (125 g). The mixture is then stirred and hydrogenated, keeping the temperature below 40 by regulation of the stirring rate and input of hydrogen gas. After the addition is complete, the mixture is filtered. The filtrate containing <strong>[35613-44-6]methyl 2-aminophenylacetate</strong> is cooled to -20 and triethylamine (3.75 kg) is added all at once with stirring. This is followed by the slow addition of a solution of methanesulfonyl chloride (3.91 kg) in toluene (4.5L), keeping the temperature between -2 and 5. After stirring at -2 for 1 hour, the mixture is filtered and washed with toluene (10 l). The filter cake is then slurried with water (90 l) for 90 minutes, filtered, and washed with water (45 l) and methanol (8 l). The solid is dried at 50 in vacuo overnight to yield methyl 2-(methylsulfonylamino)phenylacetate, mp 73-75.
  • 4
  • [ 30095-98-8 ]
  • [ 114953-81-0 ]
  • 6
  • [ 30095-98-8 ]
  • [ 15121-84-3 ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate; In tetrahydrofuran; methanol; for 6h;Reflux; General procedure: To a mixture of LiAlH4 (15 mmol) in anhydrous THF (25 mL) in an ice-bath was added dropwise a solution of phenylacetic acids (15 mmol) in THF (8 mL). This mixture was stirred at room temperature for 30 min, and then heated to reflux for 4 h. After it was cooled to room temperature, water (0.5 mL) was added, and then NaOH (15percent, 0.5 mL) and water (1.5 mL) were added in sequence. After stirring for another 30 min, the mixture was filtered, dried over anhydrous Na2SO4 and concentrated to give crude products. Pure phenylethyl alcohols were obtained in 50-85percent yield by column chromatography. Alternative method: To a solution of phenylacetic acids (15 mmol) in MeOH (30 mL) was added SOCl2 (30 mmol). This mixture was heated to reflux for 3 h before evaporation. The residue was dissolved in DCM (30 mL), washed with aqueous NaHCO3, water and brine, dried over anhydrous Na2SO4, and concentrated to give 100percent yield of crude methyl phenylacetates which were used to next step without further purification. To a solution of the methyl phenylacetates in THF (30 mL) was added NaBH4 (60 mmol). When the mixture was heated to gently reflux, MeOH (1.0 mL) was added dropwise from a syringe over 5 min. After refluxing for another 6 h, the mixture was cooled to room temperature and poured into 30 mL ice water, and extracted with EtOAc (30 mL × 2). The combined organic phase was washed with brine, dried over anhydrous Na2SO4, and concentrated to give crude products. Pure phenylethyl alcohols were obtained in 70-85percent yield by column chromatography.
  • 7
  • [ 30095-98-8 ]
  • [ 205383-87-5 ]
 

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