Home Cart 0 Sign in  

[ CAS No. 153775-33-8 ]

{[proInfo.proName]} ,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 153775-33-8
Chemical Structure| 153775-33-8
Structure of 153775-33-8 * Storage: {[proInfo.prStorage]}

Quality Control of [ 153775-33-8 ]

Related Doc. of [ 153775-33-8 ]

SDS
Alternatived Products of [ 153775-33-8 ]
Alternatived Products of [ 153775-33-8 ]

Product Details of [ 153775-33-8 ]

CAS No. :153775-33-8 MDL No. :MFCD04115713
Formula : C7H3F2NO4 Boiling Point : 344.4°C at 760 mmHg
Linear Structure Formula :- InChI Key :-
M.W :203.10 g/mol Pubchem ID :2782822
Synonyms :

Safety of [ 153775-33-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 153775-33-8 ]

  • Upstream synthesis route of [ 153775-33-8 ]
  • Downstream synthetic route of [ 153775-33-8 ]

[ 153775-33-8 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 67-56-1 ]
  • [ 153775-33-8 ]
  • [ 125568-71-0 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogenchloride In 1,4-dioxane for 16 h; Heating / reflux Step 1:To a solution of 2,4-difluoro-5-nitrobenzoic acid (4.96 g, 24.4 mmol, 1 eq) in MeOH (100 mL), was added a solution of 4N HCI in 1 ,4-dioxane (9 ml_). The reaction mixture was heated to reflux for 16 h, then cooled to RT and the MeOH was evaporated under vacuum. The residue was dissolved in EtOAc (50 mL) and the organic phase was washed with aqueous saturated NaHCO3 (25 mL) and brine (25 mL), then dried over MgSO4, filtered and concentrated. A quantitative yield of the ester 3a was obtained as a yellow solid (5.30 g, 24.4 mmol).
93% at 65℃; for 40 h; 2,4-difluoro-5-nitrobenzoic acid (25.00 g, 123 mmol) was dissolved in MeOH (300 mL). Sulfuric acid (0.7 mL, 12.3 mmol, 0.1 eq) was added dropwise. The reaction was heated to 65 °C for 40 h. The reaction mixture was cooled and concentrated under reduced pressure. The residue was taken up into DCM (100 mL) and washed with water (50 mL), aqueous saturated NaHC03solution (50 mL) and brine (50 mL). The aqueous layer was back-extracted with DCM (2 x 50 mL). The combined organic phases were dried over Na2S04, filtered and concentrated under reduced pressure to afford 25.21g of the desired product as a light brown solid. Yield: 93percent in 99percent purity.
92% for 15 h; Heating / reflux Preparation of methyl 2,4-difluoro-5-nitrobenzoate (Chem. Abstr. Reg. No. 125568-71-0); 2,4-Difluoro-5-nitrobenzoic acid (33.0 g, 162 mmol) was dissolved in 400 mL anhydrous methanol under an argon atmosphere, added 4 mL concentrated sulfuric acid, then heated to reflux for 15 hours. The solution was cooled and concentrated in vacuo. Redissolved in 400 mL diethyl ether, washed with sat. sodium bicarbonate (3 x 200 mL), brine, dried with magnesium sulfate, filtered and concentrated to yield title compound. (32.6 g, 92percent) APCI" 217.0; Anal. HPLC Retention time = 15.7 minutes (>99percent pure).
85% for 18 h; Heating / reflux Sulfuric acid (3 mL) was added to a solution of 2,4-dιfluoro-5-nιtrobenzoιc acid intermediate 17(100 g, 049 mol, 1 equiv) in methanol (700 mL) and the reaction heated to reflux for 18 h The reaction mixture was concentrated and the residue taken up in water and brought to pH 8 by addition of 1N NaOH The product was extracted into ethyl acetate, dried over Na2SO4, filtered and concentrated The residue was purified by silica gel flash column chromatography (0 --> 25percent EtOAc Hexanes) to give intermediate 18 (90 g, 85percent yield) as a tan solid1H NMR (400 MHz, DMSO-cfe) δ ppm 8 56 - 8 64 (m, 1 H), 7 83 - 7 94 (m, 1 H), 3 85 - 3 92 (m, 3 H)
85% for 18 h; Heating / reflux Intermediate 17; methyl 2,4-difluoro-5-nitrobenzoate; <n="24"/>Sulfuric acid (3 mL) was added to a solution of 2,4-difluoro-5-nitrobeπzoic acid intermediate 16 (100 g, 0.49 mol, 1 equiv) in methanol (700 mL) and the reaction heated to reflux for 18 h. The reaction mixture was concentrated and the residue taken up in water and brought to pH 8 by addition of 1 N NaOH. The product was extracted into ethyl acetate, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash column chromatography (0 --> 25percent EtOAc: Hexanes) to give intermediate. 7 (90 g, 85percent yield) as a tan solid. 1H NMR (400 MHz, DMSO-cfe) δ ppm 8.56 - 8.64 (m, 1 H), 7.83 - 7.94 (m, 1 H), 3.85 - 3.92 (m, 3 H).
85% for 18 h; Heating / reflux Intermediate 2; methyl 2,4-difluoro-5-nitrobenzoate; <n="13"/>Sulfuric acid (3 mL) was added to a solution of 2,4-difluoro-5-nitrobenzoic acid intermediate 1 (100 g, 0.49 mol, 1 equiv) in methanol (700 mL) and the reaction heated to reflux for 18 h. The reaction mixture was concentrated and the residue taken up in water and brought to pH 8 by addition of 1N NaOH. The product was extracted into ethyl acetate, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash column chromatography (0 --> 25percent EtOAc: Hexanes) to give intermediate 2 (90 g, 85percent yield) as a tan solid.1H NMR (400 MHz, DMSO-Cf6) δ ppm 8.56 - 8.64 (m, 1 H), 7.83 - 7.94 (m, 1 H), 3.85 - 3.92 (m, 3 H).

Reference: [1] Patent: WO2007/19674, 2007, A1, . Location in patent: Page/Page column 45
[2] Patent: JP2018/508527, 2018, A, . Location in patent: Paragraph 0212; 0213
[3] Patent: WO2008/84300, 2008, A1, . Location in patent: Page/Page column 28
[4] Patent: WO2009/75960, 2009, A1, . Location in patent: Page/Page column 22
[5] Patent: WO2009/58919, 2009, A1, . Location in patent: Page/Page column 22-23
[6] Patent: WO2009/58923, 2009, A1, . Location in patent: Page/Page column 11-12
[7] Patent: US2011/201604, 2011, A1, . Location in patent: Page/Page column 116; 123
[8] Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1845 - 1854
  • 2
  • [ 153775-33-8 ]
  • [ 125568-71-0 ]
Reference: [1] Patent: WO2005/121132, 2005, A1, . Location in patent: Page/Page column 227-228
  • 3
  • [ 1583-58-0 ]
  • [ 153775-33-8 ]
YieldReaction ConditionsOperation in experiment
98% at 0 - 20℃; for 16.5 h; Step A
To a suspension of 2,4-difluorobenzoic acid (9.985 g, 63.2 mmol) in concentrated sulfuric acid (30 mL) at 0° C. was added fuming nitric acid (30 mL) over 30 min.
The mixture was allowed to warm to RT and stirred for an additional 16 h.
The homogeneous mixture was poured onto ice and extracted with ethyl acetate.
The organic extract was washed with water, dried and concentrated in vacuo to afford 2,4-difluoro-5-nitrobenzoic acid (12.56 gm, 98percent) as pale yellow solid.
98% With sulfuric acid; nitric acid In water at 20 - 50℃; for 3.5 h; Nitric Acid (120 mL) was added slowly to a cold solution of sulfuric acid (200 mL) 2,4- difluorobenzoic acid (65 g, 0 41 mol, 1 equiv) was added portionwise over 1 5 h and the reaction allowed to warm to RT The reaction mixture was heated to 50 0C for 2h and then poured slowly onto ice The product was extracted into ethyl acetate, dried over Na2SO4, filtered and concentrated to give intermediate 17 (82 g, 98percent yield) as a yellow solid 1H NMR (400 MHz, DMSO-cfe) δ ppm 8 56 (t, J=I 87 Hz, 1 H), 7 82 (t, J=10 71 Hz, 1 H)
98% at 0 - 20℃; for 16.5 h; A) To a suspension of 2,4-difluorobenzoic acid (9. 985 g, 63.2 mmol) in concentrated sulfuric acid (30 [ML)] at [0 °C] was added fuming nitric acid (30 [ML)] over 30 min. The mixture was allowed to warm to RT and stirred for additional 16 h. The homogeneous mixture was poured over ice and extracted with ethyl acetate. The organic extract was washed with water, dried and concentrated in vacuo to afford 2,4- difluoro-5-nitrobenzoic acid (12.56 gm, 98percent) as pale yellow solid.
98% at 20 - 50℃; for 3.5 h; The synthesis of intermediate 22; <n="23"/>Intermediate 16; 2,4-difluoro-5-nitrobenzoic acid; F O; Nitric Acid (120 ml.) was added slowly to a cold solution of sulfuric acid (200 mL). 2,4-difluorobenzoic acid (65 g, 0.41 mol, 1 equiv) was added portioπwise over 1.5 h and the reaction allowed to warm to RT. The reaction mixture-was heated to 50 0C for 2h and then poured slowly onto ice. The product was extracted into ethyl acetate, dried over Na2SO4, filtered and concentrated to give intermediate 16 (82 g, 98percent yield) as a yellow solid.1H NMR (400 MHz, DMSO-CZ6) δ ppm 8.56 (t, J=I, .87 Hz, 1 H), 7.82 (t, ./=10.71 Hz, 1 H).
98% at 20 - 50℃; for 3.5 h; Intermediate 1; 2,4-difluoro-5-nitrobeπzoic acid; Nitric Acid (120 mL) was added slowly to a cold solution of sulfuric acid (200 mL). 2,4- difluorobenzoic acid (65 g, 0.41 mol, 1 equiv) was added portionwise over 1.5 h and the reaction allowed to warm to RT. The reaction mixture was heated to 50 0C for 2h and then poured slowly onto ice. The product was extracted into ethyl acetate, dried overNa2SO4, filtered and concentrated to give intermediate 1 (82 g, 98percent yield) as a yellow solid.1H NMR (400 MHz, DMSO-dβ) δ ppm 8.56 (t, J=7.87 Hz, 1 H), 7.82 (t, J=10.71 Hz, 1 H).
61% With nitric acid In sulfuric acid 2,4-Difluoro-5-nitrobenzoic acid
2,4-Difluorobenzoic acid (5 g, 0.031 M) was dissolved in concentrated sulfuric acid (30 ml), and cooled to 0°.
The mixture was stirred, and fuming nitric acid (d 1.567 g/ml, 1.91 ml, 0.047 M) added dropwise, keeping the temperature below 5°.
After stirring for 3 hours, the mix was poured onto ice, and organics extracted into dichloromethane (2*75 ml).
The combined organic layers were washed with water, dried (MgSO4), and evaporated to give 2,4-difluoro-5-nitrobenzoic acid (3.9 g, 61percent).
Nmr (DMSO-d6): δ7.18 (t, 1H); 8.88 (t, 1H); 9.93 (br, 1H).

Reference: [1] Patent: US2004/77696, 2004, A1, . Location in patent: Page/Page column 9
[2] Patent: WO2009/75960, 2009, A1, . Location in patent: Page/Page column 21
[3] Patent: WO2004/13145, 2004, A1, . Location in patent: Page 41
[4] Patent: WO2009/58919, 2009, A1, . Location in patent: Page/Page column 21-22
[5] Patent: WO2009/58923, 2009, A1, . Location in patent: Page/Page column 11
[6] Journal of Medicinal Chemistry, 2003, vol. 46, # 10, p. 1905 - 1917
[7] Patent: US5478820, 1995, A,
[8] Journal of Agricultural and Food Chemistry, 1996, vol. 44, # 11, p. 3643 - 3652
[9] Patent: US2012/108583, 2012, A1, . Location in patent: Page/Page column 22
  • 4
  • [ 1583-58-0 ]
  • [ 153775-33-8 ]
Reference: [1] Patent: US5910498, 1999, A,
Historical Records

Related Functional Groups of
[ 153775-33-8 ]

Aryls

Chemical Structure| 317-46-4

[ 317-46-4 ]

2-Fluoro-3-nitrobenzoic acid

Similarity: 0.99

Chemical Structure| 453-71-4

[ 453-71-4 ]

4-Fluoro-3-nitrobenzoic acid

Similarity: 0.94

Chemical Structure| 946126-94-9

[ 946126-94-9 ]

Methyl 2-fluoro-3-nitrobenzoate

Similarity: 0.92

Chemical Structure| 331765-71-0

[ 331765-71-0 ]

3,5-Difluoro-2-nitrobenzoic acid

Similarity: 0.91

Chemical Structure| 1000339-51-4

[ 1000339-51-4 ]

3-Fluoro-2-nitrobenzoic acid

Similarity: 0.91

Fluorinated Building Blocks

Chemical Structure| 317-46-4

[ 317-46-4 ]

2-Fluoro-3-nitrobenzoic acid

Similarity: 0.99

Chemical Structure| 453-71-4

[ 453-71-4 ]

4-Fluoro-3-nitrobenzoic acid

Similarity: 0.94

Chemical Structure| 946126-94-9

[ 946126-94-9 ]

Methyl 2-fluoro-3-nitrobenzoate

Similarity: 0.92

Chemical Structure| 331765-71-0

[ 331765-71-0 ]

3,5-Difluoro-2-nitrobenzoic acid

Similarity: 0.91

Chemical Structure| 1000339-51-4

[ 1000339-51-4 ]

3-Fluoro-2-nitrobenzoic acid

Similarity: 0.91

Nitroes

Chemical Structure| 317-46-4

[ 317-46-4 ]

2-Fluoro-3-nitrobenzoic acid

Similarity: 0.99

Chemical Structure| 453-71-4

[ 453-71-4 ]

4-Fluoro-3-nitrobenzoic acid

Similarity: 0.94

Chemical Structure| 946126-94-9

[ 946126-94-9 ]

Methyl 2-fluoro-3-nitrobenzoate

Similarity: 0.92

Chemical Structure| 331765-71-0

[ 331765-71-0 ]

3,5-Difluoro-2-nitrobenzoic acid

Similarity: 0.91

Chemical Structure| 1000339-51-4

[ 1000339-51-4 ]

3-Fluoro-2-nitrobenzoic acid

Similarity: 0.91

Carboxylic Acids

Chemical Structure| 317-46-4

[ 317-46-4 ]

2-Fluoro-3-nitrobenzoic acid

Similarity: 0.99

Chemical Structure| 453-71-4

[ 453-71-4 ]

4-Fluoro-3-nitrobenzoic acid

Similarity: 0.94

Chemical Structure| 331765-71-0

[ 331765-71-0 ]

3,5-Difluoro-2-nitrobenzoic acid

Similarity: 0.91

Chemical Structure| 1000339-51-4

[ 1000339-51-4 ]

3-Fluoro-2-nitrobenzoic acid

Similarity: 0.91

Chemical Structure| 1131580-60-3

[ 1131580-60-3 ]

3,5-Difluoro-4-nitrobenzoic acid

Similarity: 0.89