Home Cart 0 Sign in  
X

[ CAS No. 13671-00-6 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 13671-00-6
Chemical Structure| 13671-00-6
Chemical Structure| 13671-00-6
Structure of 13671-00-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 13671-00-6 ]

Related Doc. of [ 13671-00-6 ]

Alternatived Products of [ 13671-00-6 ]

Product Details of [ 13671-00-6 ]

CAS No. :13671-00-6 MDL No. :MFCD00051778
Formula : C8H6F2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :QNPFLTKQLFSKBY-UHFFFAOYSA-N
M.W : 172.13 Pubchem ID :518798
Synonyms :

Calculated chemistry of [ 13671-00-6 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 2
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 37.64
TPSA : 26.3 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.96 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.0
Log Po/w (XLOGP3) : 1.96
Log Po/w (WLOGP) : 2.59
Log Po/w (MLOGP) : 2.79
Log Po/w (SILICOS-IT) : 2.54
Consensus Log Po/w : 2.37

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.38
Solubility : 0.718 mg/ml ; 0.00417 mol/l
Class : Soluble
Log S (Ali) : -2.14
Solubility : 1.25 mg/ml ; 0.00729 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.03
Solubility : 0.162 mg/ml ; 0.00094 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.27

Safety of [ 13671-00-6 ]

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

Application In Synthesis of [ 13671-00-6 ]

* 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 [ 13671-00-6 ]
  • Downstream synthetic route of [ 13671-00-6 ]

[ 13671-00-6 ] Synthesis Path-Upstream   1~17

  • 1
  • [ 67-56-1 ]
  • [ 372-18-9 ]
  • [ 68-12-2 ]
  • [ 437-81-0 ]
  • [ 13671-00-6 ]
YieldReaction ConditionsOperation in experiment
58%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h;
Stage #2: at -78 - 20℃; for 2 h;
General procedure: n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in THF (3 mL) at -78 °C for 30 min. Then, DMF (0.22 mL, 2.2 mmol) was added to the mixture and the obtained mixture was stirred at rt. After 2 h at the same temperature, THF was removed. Then, MeOH (3 mL) was added to the residue and the mixture was stirred at room temperature. After 30 min, I2 (1523 mg, 6 mmol) and K2CO3 (829 mg, 6 mmol) were added at 0 °C and the obtained mixture was stirred for 22 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3.x.20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide methyl 4-methoxy-1-benzoate in 82percent yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure methyl 4-methoxybenzoate as a colorless oil.
Reference: [1] Tetrahedron, 2012, vol. 68, # 24, p. 4701 - 4709
  • 2
  • [ 67-56-1 ]
  • [ 385-00-2 ]
  • [ 13671-00-6 ]
YieldReaction ConditionsOperation in experiment
82% for 6 h; Reflux General procedure: A catalytic amount of concentrated H2SO4 wasadded to a solution of carboxylic acids 16(a–j) (1.0 mmol)in 50 mL of methanol, and the mixture was refluxed for 6 h. It was allowed to cool. The saturated solution ofNaHCO3 was added to the reaction mixture, and it wasextracted with EtOAc (2 X 50 mL). The combined organiclayer was dried Na2SO4 and concentrated to obtain puremethyl esters 17(a–j).
75.9% Inert atmosphere; Reflux To a suspension of 2,6-difluorobenzoic acid (50 g, 316 mmol) in MeOH (800 mL) was added TsOH ( 6 g, 10percent), the mixture was heated to reflux overnight. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc and washed with saturated NaHCO3 and brinesuccessively. The organic layer was separated, dried over Na2SO and concentrated under reduced pressure to give methyl 2,6-difluorobenzoate. 41 g (75.9percent yield) 1 H NMR (400 MHz, CDCI3) δ ppm 7.37-7.46 (m, 1 H), 6.91 - 6.98 (m, 2H), 3.95 (s, 3H).
73%
Stage #1: for 2 h; Reflux
Stage #2: at 20℃; for 2 h;
Step 2: methyl 2,6-difluorobenzoateTo a solution of 2,6-difluorobenzoic acid (100 g, 0.63 mol) in sulfurous dichloride (150 mL) and the resulting reaction mixture was heated to refluxing for 2 hrs. Sulfurous dichloride was removed in vacuo, the residue in pyridine (100 ml) was added MeOH (100 mL) slowly and stirred at room temperature for 2 hrs. The solvent was removed in vacuo, the residue was dissolved in EtOAc (200 mL) and washed with aqueous NaOH (IN), HC1 (IN) and brine. The solution was dried over Na2S04, filtered and concentrated to afford the desired product (78.8 g, 73percent).1H NMR (CDCI3): ? 7.46-7.38 (1H, m), 6.98-9.93 (2H, m), 3.95 (3H, d, J = 2.0 Hz).
73%
Stage #1: for 2 h; Reflux
Stage #2: for 2 h; Reflux
2,6-difluorobenzoic acid (10 (^, 0.63111001) was dissolved in thionyl chloride (1501 ^), and the resulting mixture was heated under reflux for 2 hours. The excess sodium sulfoxide was distilled off and the resulting residue (100 mL) was added dropwise and the methanol was slowly added dropwise (100 mL). The reaction was stirred at room temperature for 2 hours and the solvent was removed in vacuo to remove the solvent. The resulting oil was dissolved in 200 mL of ethyl acetate and treated with IN sodium hydroxide solution, IN hydrochloric acid , Water and saturated salt water. After evaporation of the solvent in vacuo, the title compound (78.8 g, 73percent) was obtained as an oil.
71% at 20℃; Reflux To a solution of 2,6-difluorobenzoic acid (30.0 g, 190.0 mmol) in MeOH (100 mL) was added concentrated sulfuric acid (5 mL) dropwise at room temperature. The reaction mixture was heated under reflux overnight. The solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give 1 (23.2 g, 71percent) as a yellow oil. 1H NMR (CDCl3): δ 7.45–7.39 (m, 1H), 6.98–6.93 (m, 2H), 3.96 (s, 3H).

Reference: [1] Organic Process Research and Development, 2016, vol. 20, # 2, p. 233 - 241
[2] Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643
[3] Patent: WO2011/59610, 2011, A1, . Location in patent: Page/Page column 101-102
[4] Patent: WO2013/71865, 2013, A1, . Location in patent: Page/Page column 25
[5] Patent: CN103102349, 2017, B, . Location in patent: Paragraph 0147-0149
[6] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 4, p. 1017 - 1021
  • 3
  • [ 67-56-1 ]
  • [ 372-18-9 ]
  • [ 68-12-2 ]
  • [ 437-81-0 ]
  • [ 13671-00-6 ]
YieldReaction ConditionsOperation in experiment
58%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h;
Stage #2: at -78 - 20℃; for 2 h;
General procedure: n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in THF (3 mL) at -78 °C for 30 min. Then, DMF (0.22 mL, 2.2 mmol) was added to the mixture and the obtained mixture was stirred at rt. After 2 h at the same temperature, THF was removed. Then, MeOH (3 mL) was added to the residue and the mixture was stirred at room temperature. After 30 min, I2 (1523 mg, 6 mmol) and K2CO3 (829 mg, 6 mmol) were added at 0 °C and the obtained mixture was stirred for 22 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3.x.20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide methyl 4-methoxy-1-benzoate in 82percent yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure methyl 4-methoxybenzoate as a colorless oil.
Reference: [1] Tetrahedron, 2012, vol. 68, # 24, p. 4701 - 4709
  • 4
  • [ 67-56-1 ]
  • [ 385-00-2 ]
  • [ 13671-00-6 ]
  • [ 501433-14-3 ]
Reference: [1] European Journal of Organic Chemistry, 2002, # 19, p. 3351 - 3358
  • 5
  • [ 28177-48-2 ]
  • [ 13671-00-6 ]
Reference: [1] Journal of the Chemical Society, Chemical Communications, 1987, # 12, p. 904 - 905
  • 6
  • [ 67-56-1 ]
  • [ 437-81-0 ]
  • [ 13671-00-6 ]
Reference: [1] Organic Process Research and Development, 2012, vol. 16, # 5, p. 1082 - 1089
  • 7
  • [ 372-18-9 ]
  • [ 13671-00-6 ]
Reference: [1] European Journal of Organic Chemistry, 2002, # 19, p. 3351 - 3358
[2] Journal of Medicinal Chemistry, 1968, vol. 11, # 4, p. 814 - 819
  • 8
  • [ 385-00-2 ]
  • [ 13671-00-6 ]
Reference: [1] Journal of Medicinal Chemistry, 1968, vol. 11, # 4, p. 814 - 819
  • 9
  • [ 437-81-0 ]
  • [ 13671-00-6 ]
Reference: [1] Green Chemistry, 2018, vol. 20, # 17, p. 3931 - 3943
  • 10
  • [ 67-56-1 ]
  • [ 13671-00-6 ]
Reference: [1] Journal of Organic Chemistry, 2002, vol. 67, # 5, p. 1703 - 1704
  • 11
  • [ 18107-18-1 ]
  • [ 385-00-2 ]
  • [ 13671-00-6 ]
Reference: [1] Green Chemistry, 2018, vol. 20, # 17, p. 3931 - 3943
  • 12
  • [ 35367-38-5 ]
  • [ 124-41-4 ]
  • [ 13671-00-6 ]
  • [ 140-38-5 ]
Reference: [1] Collection of Czechoslovak Chemical Communications, 1989, vol. 54, # 5, p. 1363 - 1369
  • 13
  • [ 67-56-1 ]
  • [ 18063-02-0 ]
  • [ 13671-00-6 ]
  • [ 385-00-2 ]
Reference: [1] Journal of Physical Organic Chemistry, 2012, vol. 25, # 3, p. 267 - 270
  • 14
  • [ 67-56-1 ]
  • [ 18063-02-0 ]
  • [ 13671-00-6 ]
Reference: [1] Journal of Medicinal Chemistry, 1968, vol. 11, # 4, p. 814 - 819
[2] Journal of Physical Organic Chemistry, 2012, vol. 25, # 3, p. 267 - 270
  • 15
  • [ 13671-00-6 ]
  • [ 84832-01-9 ]
YieldReaction ConditionsOperation in experiment
100% at 20℃; for 2 h; Step 3: methyl 2,6-difluoro-3-nitrobenzoateTo a solution of methyl 2,6-difluorobenzoate (68.8 g, 0.4 mol) in con. H2SO4 (300 mL) was added potassium nitroperoxous acid (48.5 g, 0.48 mol) for three times and the resulting reaction mixture was stirred at room temperature for 2 hrs. The mixture was droped into ice-water (500 mL) and filtered. The solid was washed with water and dried to afford the desired product (89 g, 100percent).1H NMR (DMSC i): ? 8.49-8.43 (1H, m), 7.56-7.51 (1H, m), 3.95 (3H, s).
100% at 20℃; for 2 h; The 2, 6 - difluoro-benzoic acid methyl ester (68.8g, 0.4 µM) dissolved in concentrated sulfuric acid (300 ml) in, addition of potassium nitrate (48.5g, 0 . 48 µM), continuing stirring at room temperature 2 hours. The resulting reaction solution is poured into crushed ice in slow, filtering, the resulting solid with a large number of washing and drying can be obtained as shown in the title compound (89g, 100percent)
98% at 0℃; for 1 h; To a solution of compound 1 (21.0 g, 122.0 mmol) in concentrated sulfuric acid (50 mL) was added fuming nitric acid (8 mL) dropwise at 0 °C. After the reaction mixture was stirred at 0 °C for 1 h, it was poured into ice-water. The precipitate was collected by filtration and rinsed with water to give 2 (26.0 g, 98percent) as a white solid, mp 58–60 °C. 1H NMR (CDCl3): δ 8.25–8.22 (m, 1H), 7.15–7.11 (m, 1H), 4.01 (s, 3H).
80.6% at 0℃; for 0.5 h; Fuming nitric acid (1 1 g, 174 mmol) was added to a solution of methyl 2,6- difluorobenzoate (25 g, 145 mmol) in concentrated sulfuric acid (50 ml_) at 0 °C, and the reaction was stirred for 30 min at 0°C. The reaction mixture was poured over ice-water. The precipitate was filtered to give the title compound 25.1 g (80.6 percent yield) 1H NMR (400 MHz, CDCI3) δ ppm 8.13-8.20 (m, 1 H), 7.02-7.10 (m, 1 H), 3.93 (s, 3H).
64% at 20℃; for 1 h; Cooling with ice Sulfuric acid (37 mL) was slowly added to nitric acid (20 mL) under ice-cooling, and added methyl 2,6-difluorobenzoate (25.7 g,149 mmol), The reaction was gradually warmed to room temperature and stirring was continued for 1 hour. The reaction system was poured into ice-water and filtered to obtain a white solid compound P'(20.7 g, yield 64percent).
64% at 20℃; for 1 h; Cooling with ice Sulfuric acid (37 mL) was slowly added to nitric acid (20 mL) under ice-cooling, and methyl 2,6-difluorobenzoate (25.7 g, 149 mmol) and the reaction was gradually allowed to warm to room temperature. Stirring was continued for 1 hour, The reaction system was poured into ice-water and filtered to give a white solid compound d (20.7g, yield 64percent)

Reference: [1] Patent: WO2013/71865, 2013, A1, . Location in patent: Page/Page column 26
[2] Patent: CN103102349, 2017, B, . Location in patent: Paragraph 0150-0153
[3] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 4, p. 1017 - 1021
[4] Patent: WO2011/59610, 2011, A1, . Location in patent: Page/Page column 102
[5] Patent: CN104003979, 2016, B, . Location in patent: Paragraph 0385-0387
[6] Patent: CN103923088, 2016, B, . Location in patent: Paragraph 0214; 0216-0218
[7] Patent: WO2009/134850, 2009, A1, . Location in patent: Page/Page column 16
[8] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2620 - 2623
[9] Patent: US2010/305133, 2010, A1, . Location in patent: Page/Page column 12
  • 16
  • [ 13671-00-6 ]
  • [ 1103234-56-5 ]
Reference: [1] Patent: WO2013/71865, 2013, A1,
[2] Patent: CN103102349, 2017, B,
  • 17
  • [ 13671-00-6 ]
  • [ 346691-23-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2620 - 2623
[2] Patent: CN104003979, 2016, B,
[3] Patent: CN103923088, 2016, B,
[4] Patent: US2010/305133, 2010, A1,
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 13671-00-6 ]

Fluorinated Building Blocks

Chemical Structure| 19064-14-3

[ 19064-14-3 ]

Ethyl 2,6-difluorobenzoate

Similarity: 0.97

Chemical Structure| 1415124-73-0

[ 1415124-73-0 ]

Methyl 3,5-difluoro-4-formylbenzoate

Similarity: 0.95

Chemical Structure| 586374-04-1

[ 586374-04-1 ]

Methyl 2-fluoro-3-methylbenzoate

Similarity: 0.95

Chemical Structure| 106614-28-2

[ 106614-28-2 ]

Methyl 2,4-difluorobenzoate

Similarity: 0.95

Chemical Structure| 197516-57-7

[ 197516-57-7 ]

Methyl 2-fluoro-6-methylbenzoate

Similarity: 0.93

Aryls

Chemical Structure| 19064-14-3

[ 19064-14-3 ]

Ethyl 2,6-difluorobenzoate

Similarity: 0.97

Chemical Structure| 1415124-73-0

[ 1415124-73-0 ]

Methyl 3,5-difluoro-4-formylbenzoate

Similarity: 0.95

Chemical Structure| 586374-04-1

[ 586374-04-1 ]

Methyl 2-fluoro-3-methylbenzoate

Similarity: 0.95

Chemical Structure| 106614-28-2

[ 106614-28-2 ]

Methyl 2,4-difluorobenzoate

Similarity: 0.95

Chemical Structure| 197516-57-7

[ 197516-57-7 ]

Methyl 2-fluoro-6-methylbenzoate

Similarity: 0.93

Esters

Chemical Structure| 19064-14-3

[ 19064-14-3 ]

Ethyl 2,6-difluorobenzoate

Similarity: 0.97

Chemical Structure| 1415124-73-0

[ 1415124-73-0 ]

Methyl 3,5-difluoro-4-formylbenzoate

Similarity: 0.95

Chemical Structure| 586374-04-1

[ 586374-04-1 ]

Methyl 2-fluoro-3-methylbenzoate

Similarity: 0.95

Chemical Structure| 106614-28-2

[ 106614-28-2 ]

Methyl 2,4-difluorobenzoate

Similarity: 0.95

Chemical Structure| 197516-57-7

[ 197516-57-7 ]

Methyl 2-fluoro-6-methylbenzoate

Similarity: 0.93