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Product Details of [ 3113-71-1 ]

CAS No. :3113-71-1 MDL No. :MFCD00007168
Formula : C8H7NO4 Boiling Point : -
Linear Structure Formula :- InChI Key :XDTTUTIFWDAMIX-UHFFFAOYSA-N
M.W : 181.15 Pubchem ID :18370
Synonyms :

Calculated chemistry of [ 3113-71-1 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 2
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 47.19
TPSA : 83.12 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.73 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.1
Log Po/w (XLOGP3) : 2.36
Log Po/w (WLOGP) : 1.6
Log Po/w (MLOGP) : 0.84
Log Po/w (SILICOS-IT) : -0.47
Consensus Log Po/w : 1.09

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -2.66
Solubility : 0.397 mg/ml ; 0.00219 mol/l
Class : Soluble
Log S (Ali) : -3.75
Solubility : 0.0325 mg/ml ; 0.00018 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.54
Solubility : 5.24 mg/ml ; 0.0289 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.64

Safety of [ 3113-71-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 3113-71-1 ]

* 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.

  • Upstream synthesis route of [ 3113-71-1 ]
  • Downstream synthetic route of [ 3113-71-1 ]

[ 3113-71-1 ] Synthesis Path-Upstream   1~30

  • 1
  • [ 3113-71-1 ]
  • [ 61700-61-6 ]
Reference: [1] Chemical Communications, 2012, vol. 48, # 94, p. 11558 - 11560
[2] Patent: US2012/277224, 2012, A1,
  • 2
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  • [ 7697-29-2 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1867, vol. 144, p. 182
  • 3
  • [ 89-87-2 ]
  • [ 18515-67-8 ]
  • [ 3113-71-1 ]
  • [ 80866-75-7 ]
Reference: [1] Patent: CN105237317, 2016, A, . Location in patent: Paragraph 0079; 0080
  • 4
  • [ 3113-71-1 ]
  • [ 18515-67-8 ]
Reference: [1] Tetrahedron, 2008, vol. 64, # 11, p. 2586 - 2595
[2] Patent: US2013/310394, 2013, A1,
  • 5
  • [ 99-04-7 ]
  • [ 3113-72-2 ]
  • [ 3113-71-1 ]
  • [ 5437-38-7 ]
Reference: [1] Journal of the Chinese Chemical Society, 2014, vol. 61, # 12, p. 1307 - 1312
[2] Tetrahedron Letters, 2006, vol. 47, # 49, p. 8651 - 8652
[3] Tetrahedron Letters, 2008, vol. 49, # 28, p. 4449 - 4451
[4] Tetrahedron Letters, 2011, vol. 52, # 13, p. 1452 - 1455
  • 6
  • [ 99-04-7 ]
  • [ 3113-72-2 ]
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  • [ 5437-38-7 ]
  • [ 3478-09-9 ]
Reference: [1] Tetrahedron Letters, 2008, vol. 49, # 28, p. 4449 - 4451
  • 7
  • [ 99-04-7 ]
  • [ 3113-72-2 ]
  • [ 3113-71-1 ]
Reference: [1] Chemische Berichte, 1907, vol. 40, p. 4413
[2] Chemische Berichte, 1905, vol. 38, p. 3555
[3] Chemische Berichte, 1909, vol. 42, p. 433
  • 8
  • [ 99-04-7 ]
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  • [ 5437-38-7 ]
Reference: [1] Journal of the Chinese Chemical Society, 2014, vol. 61, # 12, p. 1307 - 1312
[2] Tetrahedron Letters, 2006, vol. 47, # 49, p. 8651 - 8652
[3] Tetrahedron Letters, 2008, vol. 49, # 28, p. 4449 - 4451
[4] Tetrahedron Letters, 2011, vol. 52, # 13, p. 1452 - 1455
  • 9
  • [ 99-04-7 ]
  • [ 3113-72-2 ]
  • [ 3113-71-1 ]
  • [ 5437-38-7 ]
  • [ 3478-09-9 ]
Reference: [1] Tetrahedron Letters, 2008, vol. 49, # 28, p. 4449 - 4451
  • 10
  • [ 99-04-7 ]
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  • [ 5437-38-7 ]
Reference: [1] Chemische Berichte, 1907, vol. 40, p. 4413
[2] Chemische Berichte, 1909, vol. 42, p. 433
  • 11
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YieldReaction ConditionsOperation in experiment
96.1% With thionyl chloride In ethanol at 0 - 80℃; for 2 h; The 3 - methyl -4 - nitro benzoic acid (18.1 g, 100 mmol) is added to a 500 ml three-necked flask in the dry, add 200 ml anhydrous ethanol, then ice bath to 0 °C, 10 ml thionyl chloride slowly dropping into the three-port in the bottle, the bottle to maintain the three temperature not exceeding 10 °C, the completion of the dropping, the reaction temperature is slowly by the 0 °C gradually rose to 80 °C, tail gas for the absorption of aqueous solution of sodium hydroxide, the reaction 2 h is finished, the completion of the reaction, reducing pressure and methanol and the remaining thionyl chloride, to obtain white solid 20.1 g of the compound (2),Yield: 96.1percent
Reference: [1] Patent: CN108329269, 2018, A, . Location in patent: Paragraph 0087-0092
  • 12
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  • [ 75-03-6 ]
  • [ 30650-90-9 ]
YieldReaction ConditionsOperation in experiment
91% With sodium hydrogencarbonate In N,N-dimethyl-formamide A.
Ethyl 3-methyl-4-nitrobenzoate.
A mixture of 3-methyl-4-nitrobenzoic acid (362.3 g, 2.0 mol), N,N-dimethylformamide (20OOmL), sodium bicarbonate (200 g, 2.38 mol) and iodoethane (623.9 g, 4.0 mol) was stirred at 70° C. for 18 h.
The mixture was allowed to cool to room temperature and poured into water (2000 mL).
The resulting solid was collected by filtration, washed with water and dried.
The solid was washed further with hexane and dried to provide the title product (382.1 g, 91percent) as an off-white solid, mp 51-52.5 ° C.: 1H NMR (CDCl3) d 8.04-7.98 (m, 3H), 4.42 (q, 2H), 2.63 (s, 3H), 1.42 (t, 3H); Mass spectrum (NH3-CI) m/z 210 (100percent, M+H+).
91% With sodium hydrogencarbonate In N,N-dimethyl-formamide A.
Ethyl 3-methyl-4-nitrobenzoate
A mixture of 3-methyl-4-nitrobenzoic acid (1) (362.3 g, 2.0 mol), N,N-dimethylformamide (2000 mL), sodium bicarbonate (200 g, 2.38 mol) and iodoethane (623.9 g, 4.0 mol) was stirred at 70° C. for 18 h.
The mixture was allowed to cool to room temperature and poured into water (2000 mL.
The resulting solid was collected by filtration, washed with water and dried.
The solid was washed further with hexane and dried to provide the title product (382.1 g, 91percent) as an off-white solid: mp 51°-52.5° C.; 1 H NMR (CDCl3) δ 8.04-7.98 (m, 3H), 4.42 (q, 2H), 2.63 (s, 3H), 1.42 (t, 3H); Mass spectrum (NH3 --CI) m/z 210 (100percent, M+H+).
Reference: [1] Patent: US2001/44535, 2001, A1,
[2] Patent: US5760028, 1998, A,
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Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 3, p. 1155 - 1158
[2] European Journal of Organic Chemistry, 2010, # 24, p. 4662 - 4670
[3] Justus Liebigs Annalen der Chemie, 1867, vol. 144, p. 182
[4] Chemistry - A European Journal, 2010, vol. 16, # 7, p. 2054 - 2062
[5] Journal of the American Chemical Society, 2018, vol. 140, # 39, p. 12457 - 12468
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YieldReaction ConditionsOperation in experiment
56% With potassium permanganate In pyridine; water for 72 h; Heating / reflux A mixture of 3-methyl-4-nitrobenzoic acid (150 g, 0.825 MOL), pyridine (1.5 L) and water (1.5 L) was heated to reflux. To the hot reaction mixture was added KMN04 (10 mol) portion wise and reflux for 72 h. The hot reaction mixture was filtered through celite and washed with hot water. The filtrate was concentrated under vacuum, residue diluted with water (750 ML) and acidified with concentrated HCl at 0°C. The solid obtained was filtered, washed with water and dried under vacuum to give 4-nitro isophthalic acid (98 g, 56percent). TLC, CHLOROFORIN/METHANOL, 7: 3, RIF=0. 2.
56% With pyridine; potassium permanganate In water for 72 h; Heating / reflux A mixture of 3-methyl-4-nitrobenzoic acid (150g, 0. [825MOL),] pyridine (1.5L) and water (1. 5L) was heated to reflux. To the hot reaction mixture was added [KMN04 (LOMOL) PORTION] wise and reflux for 72h. The hot reaction mixture was filtered through celite and washed with hot water. The filtrate was concentrated under vacuum, residue diluted with water (750mL) and acidified with con. [HC1] at [0°C.] The solid obtained was filtered, washed with water and dried under vacuum to give 4-nitro isophthalic acid (98g, 56percent). TLC, Chloroform/Methanol, 7: 3, [RI=0.]
40% With pyridine; potassium permanganate In water A.
Synthesis of 4-Nitro isophthalic acid
A mixture of 3-methyl-4-nitrobenzoic acid (6.3 g, 34.8 mmol), pyridine (100 mL) and water (100 mL) was heated to reflux.
To the hot reaction mixture was added KMnO4 (130 g) portion wise and refluxed for 72 h.
The reaction mixture was filtered through celite and washed with hot water.
The filtrate was concentrated under vacuum, residue diluted with water (50 mL) and acidified with concentrated HCl at 0° C.
The solid obtained was filtered, washed with water and dried under vacuum to give 4-nitro isophthalic acid in 40percent yield.
51% With potassium permanganate In water (1)
To a solution of potassium permanganate (47.5 g (0.30 mol) in 500.0 ml of water, 3-methyl-4-nitrobenzoic acid (20.0 g (0.13 mol) was added and the resulting mixture was stirred at 70° C. overnight.
Then, porassium permanganate (24.5 g (0.16 mol) was further added and the mixture was stirred at 70° C. for another two days.
The insolubles were removed by filtrering while hot, and the filtrate was made, after being cooled, acidic with concentrated hydrochloric acid to have crystals separated.
The resulting crystals were filtered and washed with water to give 11.9 g (51percent) of 4-nitroisophthalic acid as white crystals.
mp: 256.8-258.5° C.; NMR (DMSO-d6) δ: 8.07 (1H, dd, J=8.3 and 0.3 Hz), 8.27 (1H, dd, J=8.3 and 1.9 Hz), 8.34 (1H, dd, J=1.9 and 0.3 Hz), 13.80 (2H, brs).

Reference: [1] Patent: WO2005/11686, 2005, A1, . Location in patent: Page 38
[2] Patent: WO2004/7491, 2004, A1, . Location in patent: Page 56-57
[3] Patent: EP1174028, 2002, A1, . Location in patent: Example 46
[4] Patent: US2008/280900, 2008, A1,
[5] Journal fuer Praktische Chemie (Leipzig), 1888, vol. <2> 38, p. 313
[6] Patent: US6586617, 2003, B1,
  • 15
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YieldReaction ConditionsOperation in experiment
23 % With pyridine; phosphorus pentachloride; trichlorophosphate In dichloromethane Part A
Preparation of the intermediate 4-nitro-3-tolunitrile, represented by the formula:
A mixture of PCl5 (200 g, 0.96 mole) and p-toluene sulfonamide (90 g, 0.52 mole) was treated with 3-methyl-4-nitrobenzoic acid (82 g, 0.44 mole).
The reaction was stirred at room temperature for 1 hour at which time it was heated to 140°C and the POCl3 (150 ml) distilled from the mixture.
The reaction was cooled to 5°C, pyridine (200 ml) was carefully added and the mixture allowed to stand overnight.
The reaction was carefully diluted to 1 L with H2O and the mixture stirred for 3 hours.
The brown solid was filtered, washed with H2O and triturated with 5 N aqueous NaOH.
The remaining solid was filtered, washed with H2O and dried to afford 60.0 g of a powder.
The solid was stirred in 1200 ml CH2Cl2 and filtered.
The supernatant was evaporated in vacuo and the residue recrystallized from EtOH to give 35.9 g (23 percent) of 4-nitro-3-tolunitrile.
MS(FD), m/e 162 (M+).
Reference: [1] Patent: EP655439, 1995, A2,
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  • [ 96784-54-2 ]
Reference: [1] Journal of Medicinal Chemistry, 1997, vol. 40, # 18, p. 2843 - 2857
[2] Justus Liebigs Annalen der Chemie, 1867, vol. 144, p. 182
[3] Patent: WO2014/172871, 2014, A1,
  • 17
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  • [ 2486-70-6 ]
YieldReaction ConditionsOperation in experiment
96% With palladium on activated charcoal; hydrogen In methanol at 20℃; for 24 h; To a solution of 3-methyl-4-nitrobenzoic acid (100 g, 552.04 mmol) in methanol (2000 mL) was added Palladium carbon (5.0 g) at room temperature under an atmosphere of hydrogen. After stirring for 24 h at room temperature, the solids were filtered out. The filtrate was concentrated under vacuum to afford 4-amino-3- methylbenzoic acid as a light yellow solid (80 g, 96percent).
90.1% With hydrogenchloride; tetrabutylammomium bromide; iron; ammonium chloride In water at 110℃; for 2 h; In a reaction flask equipped with a reflux condenser, a thermometer and a stirrer, 3-methyl-4-nitrobenzoic acid is added36.0 g (0.2 mol) of tetrabutylammonium bromide 0.9 g (0.0028 mol) and 300 ml of water are stirred well, then 16.8 g (0.3 mol) of reduced iron powder, 3.0 g (0.056 mol) of ammonium chloride, and concentrated hydrochloric acid are added. 2 ml, heated to 110°C with stirring, refluxThe reaction was carried out for 2 hours until the reaction of 3-methyl-4-nitrobenzoic acid was complete;Cool down to 35 °C, add sodium carbonate and activated carbon to decolorize for 0.5 hours, add sodium carbonate and activated carbonThe mass of 3-methyl-4-nitrobenzoic acid is 1.5percent and the pH is alkaline. Filtrate iron mud, wash twice with 5percent sodium carbonate solution, mixCombined filter mother liquor and cleaning solution, light yellow solution;Add the above pale yellow solution to sulfuric acid, adjust the pH to slightly acidic, precipitate a white precipitate, filter and wash the filter cake.Two times, the filter cake was vacuum dried in a vacuum oven at 70°C to obtain 27.3 g of 3-methyl-4-aminobenzoic acid.The product obtained in Example 2 was analyzed by liquid chromatography. The purity of the product was 99.5percent. The melting point analyzer was used to analyze the product.The melting range was 169-172°C, and the molar yield of the product was calculated to be 90.1percent based on the raw material 3-methyl-4-nitrobenzoic acid.
90.3%
Stage #1: With sodium hydroxide In water for 0.5 h; Autoclave; Inert atmosphere
Stage #2: With ammonia; hydrogen In water at 140℃; for 5 h; Autoclave
In a 1000 ml beaker, 36.2 g (0.2 mol) of 3-methyl-4-nitrobenzoic acid and 300 ml of water were added, and the pH was adjusted with 25percent sodium hydroxide under stirring until the reaction liquid was basic;Then, the above solution was poured into a 1L autoclave, and 3.0 g of Raney nickel catalyst was added. The autoclave was capped with a locking bolt, stirring was started, nitrogen was injected into the autoclave to a pressure of 2.0 MPa, and the nitrogen inlet valve was closed. After 30 minutes, the inside pressure of the autoclave does not decrease, which proves that the autoclave is sealed intact, and each is replaced with nitrogen and hydrogen three times respectively, and the ammonia gas is charged for 2 minutes, and then pressurized with hydrogen to 3.50 MPa, at a pressure of 3.50-2.50 MPa, and a temperature of 140°C. The reaction was performed for about 5 hours until the hydrogen pressure did not decrease any more as the end point of the reaction and the reaction solution was obtained.After the reaction was completed, the temperature was lowered to room temperature, and the catalyst was filtered off. The filtrate was decolored by adding sodium carbonate and activated carbon for 0.5 hour. The amounts of sodium carbonate and activated carbon were respectively 1.5percent of the mass of 3-methyl-4-nitrobenzoic acid, and the activated carbon was filtered out. Sulfuric acid was added to the solution, the pH was adjusted to slightly acidic, a white precipitate was precipitated, and the filter cake was washed with water twice. The filter cake was vacuum dried at 70°C in a vacuum oven to obtain 27.4 g of 3-methyl-4-aminobenzoic acid.FIG. 1 is a nuclear magnetic hydrogen spectrum of 3-methyl-4-aminobenzoic acid prepared in Example 1 of the present invention.As can be seen from FIG. 1 , 3-methyl-4-aminobenzoic acid was successfully prepared by the present invention.The product obtained in Example 1 was subjected to liquid chromatography and sample analysis. The purity of the product was 99.5percent. The melting point was analyzed and the melting range of the product was 169-172°C. The molar content was calculated based on the raw material 3-methyl-4-nitrobenzoic acid. The yield was 90.3percent.
84% With hydrogen In N,N-dimethyl-formamide at 25℃; for 6 h; Example 1a: 4-Amino-3-methyl-benzoic acid EPO <DP n="56"/>To a solution of 3-methyl-4-nitro-benzoic acid (100 g, 0.55 mol) in DMF (500 ml_), suspension of activated Raney Ni (50 g) in DMF (50 mL) was added and was subjected to hydrogenation (200 psi pressure and 250C) for 6 h. The reaction mixture was filtered through celite bed and was concentrated to one third of the total volume. The reaction mixture was poured into water (1300 mL) with stirring. The solid was filtered, washed with water and dried to obtain the title compound. Yield: 70 g (84percent); 1H NMR (DMSOd6, 300 MHz): δ 2.03 (s, 3H, CH3), 5.60 (s, 2H, NH2), 6.56 (d, 1 H, Ar), 7.46 (d, 1 H, Ar), 7.49 (s, 1 H, Ar); MS: m/e (ES-) 150 (M-1).

Reference: [1] Advanced Synthesis and Catalysis, 2010, vol. 352, # 9, p. 1451 - 1454
[2] Patent: WO2014/66795, 2014, A1, . Location in patent: Paragraph 0175
[3] Journal of Organic Chemistry, 2008, vol. 73, # 21, p. 8631 - 8634
[4] Patent: CN106831460, 2017, A, . Location in patent: Paragraph 0029-0059
[5] Patent: CN107501106, 2017, A, . Location in patent: Paragraph 0025-0047
[6] Patent: WO2006/51477, 2006, A2, . Location in patent: Page/Page column 53-54
[7] Organometallics, 2010, vol. 29, # 18, p. 4135 - 4138
[8] Chemische Berichte, 1909, vol. 42, p. 433
[9] Justus Liebigs Annalen der Chemie, 1867, vol. 144, p. 182
[10] Chinese Chemical Letters, 2016, vol. 27, # 1, p. 109 - 113
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YieldReaction ConditionsOperation in experiment
99% With H2 In methanol (a)
Methyl 4-amino-3-methylbenzoate. To a solution of 3-methyl-4-nitrobenzoic acid (6.50 g, 33.3 mmol) in 100 mL of MeOH was added 700 mg of 5percent Pd/C.
The mixture was hydrogenated at 48 psi H2 for 24 hours, the catalyst was removed by suction filtration, and the filtrate was concentrated under reduced pressure.
The title compound was obtained as a white solid (99percent).
1H NMR (CDCl3) δ: 2.19 (s, 3H), 3.85 (s, 3H), 4.20 (br s, 2H), 6.65 (d, 2H, J = 8.1Hz), 7.72 (d, 2H, J = 8.1Hz), 7.76 (s, 1H). Anal. (C9H11NO2) C, H, N.
Reference: [1] Patent: EP1109560, 2003, B1,
[2] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 6, p. 1107 - 1112
[3] Chemische Berichte, 1895, vol. 28, p. 597
[4] Chemical Communications, 2012, vol. 48, # 94, p. 11558 - 11560
[5] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 1, p. 81 - 84
[6] Patent: US2012/277224, 2012, A1,
[7] Zeitschrift fur Anorganische und Allgemeine Chemie, 2014, vol. 640, # 1, p. 159 - 167
[8] Patent: WO2014/66795, 2014, A1,
[9] Asian Journal of Chemistry, 2014, vol. 26, # 7, p. 1921 - 1930
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YieldReaction ConditionsOperation in experiment
96% at 0 - 80℃; for 1 h; Step 1.
Methyl 3-methyl-4-nitrobenzoate
To a solution of 3-methyl-4-nitrobenzoic acid (30 g, 165.61 mmol) in methanol (300 mL), was added thionyl chloride (25 mL) dropwise with stirring at 0° C.
After stirring for 1 h at 80° C., the resulting mixture was concentrated under vacuum to give residue, which was dissolved in petroleum ether (100 mL) and filtrated to give methyl 3-methyl-4-nitrobenzoate as a white solid (31 g, 96percent).
LC/MS (ES, m/z): [M+H]+ 196.0
1H-NMR (300 MHz, CD3Cl) δ 7.99-8.04 (m, 3H), 3.98 (s, 3H), 2.64 (s, 3H)
89% for 15 h; Reflux To a solution of 3-methyl-4-nitrobenzoic acid (25.0 g, 138 mmol) in anhydrous methanol (400 mL) was added concd H2SO4 (2 mL), at room temperature. The resulting solution was refluxed for 15 h. The reaction mixture was concentrated. The solid was filtered and washed with cold methanol and dried to obtain the ester 4 (24 g, 89percent) as a colorless solid. mp 78-80 °C.
82.3% Reflux General procedure: A mixture of organic acid (0.5 g) and methanol (100 ml) was heated under reflux in presence of sulphuric acid (0.8 ml) until the completion of the reaction which was checked by single spot TLC. Then, methanol was removed under reduced pressure a half and the solution was diluted with 20 ml of water. The product was extracted with ethyl acetate (30 ml). The organic phase was neutralized successively with NaHCO3 5percentand water, dried over anhydrous Na2SO4, and filtered. The ethyl acetate phase was separated, which on evaporation yielded the ester derivatives
37% Reflux To a solution of 2 (3-methyl-4-nitrobenzoic acid, 4.53 g, 29.98 mmol) in MeOH (25 mL) was added conc. H2SO4 (97 percent, 2.66 mL, 48.41 mmol) at room temperature. The turbid reaction mixture became clear during heating at reflux for overnight and then it was cooled to room temperature to be a suspension. The precipitates were filtered and washed with cold MeOH. Recrystallization in MeOH, filtration and drying then gave 3 (1.67 g, 37 percent) as a yellow crystalline solid. Rf: 0.5 (EtOAc:Hex =1:5); m.p. 79.5–80.0 C; IR (film, cm−1) 3118 and 3046( =C-H), 2959 (-C-H), 1732 (C=O), 1585 (Ar), 1520 (N=O), 1429 (Ar), 1344 (N=O); 1H NMR (in CDCl3, δ) 2.63 (s, 3H, CCH3), 3.96 (s, 3H, OCH3), 7.98 (s, 2H), 8.03 (s, 1H) [aromatic protons]; 13C NMR (in CDCl3, δ) 20.30 (CCH3), 52.94 (OCH3), 124.80, 128.28, 133.70, 133.96, 134.23, 152.10 (aromatic carbons), 165.56 (C=O); HR-FABMS [M+H]+ calcd for C9H10NO4 m/z 196.0610, found 196.0608.
37% at 20℃; Concentrated sulfuric acid (H2504, 97percent, 2.66 ml,48.41 mmol) is added to a solution containing the compound2 (3-methyl-4-nitrobenzoic acid, 4.53 g, 29.98 mmol) in methanol (MeOH) (25 ml) at the room temperature. After an overnight reflux under agitation, the cloudy reactant mixture becomes clear and then cooled down at the room temperature into a suspension. The precipitate is filled out and washed with cold water. A recrystallization with methanol and a filtration and drying process yields the compound 3 (1.67 g, 37percent) as yellowish solid crystals

Reference: [1] Patent: US2012/277224, 2012, A1, . Location in patent: Page/Page column 33
[2] Chemical Communications, 2012, vol. 48, # 94, p. 11558 - 11560
[3] Chemical Communications, 2007, # 5, p. 504 - 506
[4] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 14, p. 4582 - 4589
[5] Chemistry - An Asian Journal, 2010, vol. 5, # 7, p. 1573 - 1585
[6] Natural Product Research, 2018, vol. 32, # 5, p. 572 - 575
[7] Chemistry - A European Journal, 2006, vol. 12, # 26, p. 6865 - 6879
[8] Zeitschrift fur Anorganische und Allgemeine Chemie, 2014, vol. 640, # 1, p. 159 - 167
[9] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 6, p. 1107 - 1112
[10] Bulletin of the Korean Chemical Society, 2016, vol. 37, # 1, p. 7 - 12
[11] Patent: US2017/22243, 2017, A1, . Location in patent: Paragraph 0030; 0031
[12] Chemische Berichte, 1895, vol. 28, p. 597
[13] Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 10, p. 1692 - 1695
[14] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 15, p. 4416 - 4420
[15] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 1, p. 81 - 84
[16] Patent: CN105753708, 2016, A, . Location in patent: Paragraph 0003; 0006
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  • [ 3113-71-1 ]
  • [ 24078-21-5 ]
YieldReaction ConditionsOperation in experiment
95% With thionyl chloride In methanol; water a)
Methyl 3-methyl-4-nitrobenzoate
To a stirred suspension of 3-methyl-4-nitrobenzoic acid (100 g, 0.55 mole) in methanol (400 ml) was added thionyl chloride (36 g, 0.30 mole), over a period of 1 hour (the temperature of the reaction mixture rising to about 35°-40° C.).
The mixture was heated to reflux for 1.5 hours, then cooled to 50°-55° C. and maintained at this temperature for 30 minutes prior to cooling to ambient temperature.
Water (100 ml) was added over 30 minutes, with cooling applied to maintain the temperature at 20°-25° C.
Filtration was followed by washing of the solid with water (2*100 ml), and drying at 40° C. under vacuum, to afford 103 g (95percent) of methyl 3-methyl-4-nitrobenzoate as a yellow solid; m.p. 83°-85° C.; NMR (250 MHz, CDCl3), 2.62 (s, 3H, ArCH3), 3.98
(s, 3H, CO2 CH3), 8.01 (m, 3H).
95% With thionyl chloride In methanol; water d.
Methyl 3-methyl-4-nitrobenzoate
To a stirred suspension of 3-methyl-4-nitrobenzoic acid (100 g, 0.55 mole) in methanol (400 mL) was added thionyl chloride (36 g, 0.30 mole), over a period of 1 hour (the temperature of the reaction mixture rising to about 35°-40° C.).
The mixture was heated to reflux for 1.5 hours, then cooled to 50°-55° C. and maintained at this temperature for 30 minutes prior to cooling to ambient temperature.
Water (100 mL) was added over 30 minutes, with cooling applied to maintain the temperature at 20°-25° C.
Filtration was followed by washing of the solid with water (100 mL twice), and drying at 40° C. under vacuum, to afford 103 g (95percent) of methyl 3-methyl-4-nitrobenzoate as a yellow solid; mp 83°-85° C.; NMR (250 MHz, CDCl3): 2.62 (s, 3H, ArCH3), 3.98 (s, 3H, CO2 CH3), 8.01 (m, 3H).
Reference: [1] Patent: US6500405, 2002, B1,
[2] Patent: US5874466, 1999, A,
[3] Patent: US5929098, 1999, A,
[4] Patent: US5981435, 1999, A,
[5] Patent: US5280125, 1994, A,
[6] Patent: US5286740, 1994, A,
[7] Patent: EP816328, 1998, A2,
[8] Patent: EP834311, 1998, A1,
[9] Patent: EP880893, 1998, A1,
[10] Patent: EP878192, 1998, A2,
  • 21
  • [ 3240-34-4 ]
  • [ 3113-71-1 ]
  • [ 24078-21-5 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 10, p. 2027 - 2031
  • 22
  • [ 3113-71-1 ]
  • [ 74-88-4 ]
  • [ 24078-21-5 ]
Reference: [1] Patent: US4287201, 1981, A,
  • 23
  • [ 3113-71-1 ]
  • [ 77-78-1 ]
  • [ 24078-21-5 ]
Reference: [1] Asian Journal of Chemistry, 2014, vol. 26, # 7, p. 1921 - 1930
  • 24
  • [ 3113-71-1 ]
  • [ 148625-35-8 ]
Reference: [1] Chemical Communications, 2007, # 5, p. 504 - 506
  • 25
  • [ 3113-71-1 ]
  • [ 152628-03-0 ]
Reference: [1] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 6, p. 1107 - 1112
  • 26
  • [ 3113-71-1 ]
  • [ 301533-59-5 ]
Reference: [1] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 6, p. 1107 - 1112
  • 27
  • [ 67-56-1 ]
  • [ 3113-71-1 ]
  • [ 1826-67-1 ]
  • [ 180624-25-3 ]
Reference: [1] Organic Letters, 2003, vol. 5, # 16, p. 2829 - 2832
  • 28
  • [ 3113-71-1 ]
  • [ 473416-12-5 ]
Reference: [1] Patent: US2012/277224, 2012, A1,
[2] Patent: WO2014/66795, 2014, A1,
[3] Asian Journal of Chemistry, 2014, vol. 26, # 7, p. 1921 - 1930
  • 29
  • [ 3113-71-1 ]
  • [ 1092351-82-0 ]
Reference: [1] Patent: WO2014/66795, 2014, A1,
  • 30
  • [ 3113-71-1 ]
  • [ 239075-26-4 ]
Reference: [1] Chemical Communications, 2012, vol. 48, # 94, p. 11558 - 11560
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