Home Cart 0 Sign in  

[ CAS No. 949465-79-6 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 949465-79-6
Chemical Structure| 949465-79-6
Structure of 949465-79-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 949465-79-6 ]

Related Doc. of [ 949465-79-6 ]

Alternatived Products of [ 949465-79-6 ]

Product Details of [ 949465-79-6 ]

CAS No. :949465-79-6 MDL No. :MFCD22376695
Formula : C16H14ClFO4 Boiling Point : -
Linear Structure Formula :- InChI Key :KMMMWZNGDLRCHZ-UHFFFAOYSA-N
M.W : 324.73 Pubchem ID :24809620
Synonyms :

Safety of [ 949465-79-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 949465-79-6 ]

* 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.

  • Downstream synthetic route of [ 949465-79-6 ]

[ 949465-79-6 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 1011732-91-4 ]
  • [ 949465-79-6 ]
YieldReaction ConditionsOperation in experiment
89.7% Stage #1: C16H14ClFO5 With triethylsilane; trifluoroacetic acid at 0 - 15℃; for 1h; Stage #2: With sodium acetate In methanol for 3h; Heating / reflux; 2 Triethylsilane (7.50 g) was added to trifluoroacetic acid (49.02 g) that had been pre-cooled in an ice bath. Compound 3 (14.65 g) was added to the mixture keeping the temperature below 15 0C. After stirring for 1 h a solution of 17.63 g sodium acetate in 147 mL methanol was added. The mixture was heated to reflux for 3 hours then cooled to 0 0C. The slurry was filtered and the product washed with additional methanol. After drying 12.3 g of Compound 4 (89.7 % yield) was isolated: 1H NMR (DMSOd6, 400 MHz) δ 12.11 (br s, IH), 7.47 (s, IH), 7.42-7.38 (m, IH), 7.14-7.08 (m, 2H), 6.67 (s, IH), 3.87-3.84 (m, 8H)
89.7% Stage #1: C16H14ClFO5 With triethylsilane; trifluoroacetic acid at 0 - 15℃; for 1h; Stage #2: With sodium acetate In methanol at 45℃; for 2 - 3h; Heating / reflux; 2; 14 Triethylsilane (7.50 g) was added to trifluoroacetic acid (49.02 g) that had been pre-cooled in an ice bath. Compound 3 (14.65 g) was added to the mixture keeping the temperature below 15 °C. After stirring for 1 h a solution of 17.63 g sodium acetate in 147 mL methanol was added. The mixture was heated to reflux for 3 hours then cooled to 0 °C. The slurry was filtered and the product washed with additional methanol. After drying 12.3 g of Compound 4 (89.7 % yield) was isolated: 1H NMR (DMSOd6, 400 MHz) 6 12.11 (br s, IH), 7.47 (s, IH), 7.42-7.38 (m, IH), 7.14-7.08 (m, 2H), 6.67 (s, IH), 3.87-3.84 (m, 8H); Trifluoroacetic acid (10 eq.) is charged to a reactor and cooled to 0 °C. Triethylsilane (1.5 eq.) is added maintaining the temperature < 15 °C and the mixture agitated thoroughly. Compound 3 is added to the well-stirred mixture in portions maintaining the temperature < 15 °C. When the reaction is determined to be complete by HPLC, Compound 4 is precipitated by adding a solution of 5 eq. sodium acetate in methanol (13 volumes) maintaining the temperature not more than 45 °C. Warm the slurry to reflux and agitate for 2 to 3 h. The slurry is cooled to about 0 °C and then agitated at that temperature for 2 to 3 h. The product is isolated by filtration, washed with methanol and dried at about 40 °C to yield Compound 4.
With triethylsilane; trifluoroacetic acid at 0 - 15℃; for 2h; 2 Triethylsilane (6.83 g) was added to trifluoroacetic acid (33.13 g) that had been pre-cooled in an ice bath. Compound 3 (10 g) was added to the mixture keeping the temperature below 15 0C. After stirring for 2 h MTBE was added to precipitate the product. The slurry was filtered and the product washed with additional MTBE. After drying, 9.12 g of Compound 4 was isolated: 1H NMR (DMSOd6, 400 MHz) δ 12.11 (br s, IH), 7.47 (s, IH), 7.42-7.38 (m, IH), 7.14-7.08 (m, 2H), 6.67 (s, IH), 3.87-3.84 (m, 8H)
With triethylsilane; trifluoroacetic acid at 0 - 15℃; for 2h; 2 Triethylsilane (6.83 g) was added to trifluoroacetic acid (33.13 g) that had been pre-cooled in an ice bath. Compound 3 (10 g) was added to the mixture keeping the temperature below 15 °C. After stirring for 2 h MTBE was added to precipitate the product. The slurry was filtered and the product washed with additional MTBE. After drying, 9.12 g of Compound 4 was isolated: 1H NMR (DMSOd6, 400 MHz) δ 12.11 (br s, IH), 7.47 (s, IH), 7.42-7.38 (m, IH), 7.14-7.08 (m, 2H), 6.67 (s, IH), 3.87-3.84 (m, 8H).

  • 2
  • [ 949465-79-6 ]
  • [ 530-62-1 ]
  • [ 1011732-92-5 ]
YieldReaction ConditionsOperation in experiment
With 1H-imidazole In tetrahydrofuran at 20℃; 3 Imidazole (0.42 g) and l,l'-carbonyldiimidazole (5.49 g) were slurried in 30 mL of THF at ambient temperature. Compound 4 (10 g) was added in one portion and the mixture was stirred at ambient temperature until the reaction was complete by HPLC. The resulting slurry was filtered and the solids washed with MTBE. The solids were dried to yield Compound 5a: 1H NMR (DMSOd6, 400 MHz) δ 7.99 (s, IH), 7.52 (s, IH), 7.41-7.38 (m, IH), 7.30 (s, IH), 7.12-7.08 (m, 2H), 7.04 (s, IH), 6.81 (s, IH), 3.91 (s, 2H), 3.90 (s, 3H), 3.79 (s, 3H)
  • 3
  • [ 949465-79-6 ]
  • [ 949465-80-9 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride In toluene at 75℃; for 1h; 1.5 Step 5 Synthesis of 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoic acid chloride Under a nitrogen atmosphere, 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoic acid (4.7 g) was dissolved in DMF/toluene solution (25 mL) (DMF concentration: 300 ppm). Thionyl chloride (2.1 g) was added dropwise to this solution at 75°C. After stirring at 75°C for 1 hr, completion of the reaction was confirmed by HPLC. Toluene and excess thionyl chloride were evaporated under reduced pressure. Toluene (20 mL) was added to the concentrated residue, and the mixture was concentrated again under reduced pressure to give 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoic acid chloride (5.07 g). THF (15 mL) was added thereto to give a suspension of acid chloride (5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoic acid chloride) in THF, which was directly used in the next step.
  • 4
  • [ 288-32-4 ]
  • [ 949465-79-6 ]
  • [ 530-62-1 ]
  • [ 1011732-92-5 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran at 20℃; 3 Imidazole (0.42 g) and l,l'-carbonyldiimidazole (5.49 g) were slurried in 30 mL of THF at ambient temperature. Compound 4 (10 g) was added in one portion and the mixture was stirred at ambient temperature until the reaction was complete by HPLC. The resulting slurry was filtered and the solids washed with MTBE. The solids were dried to yield Compound 5a: 1H NMR (DMSOd6, 400 MHz) δ 7.99 (s, IH), 7.52 (s, IH), 7.41-7.38 (m, IH), 7.30 (s, IH), 7.12-7.08 (m, 2H), 7.04 (s, IH), 6.81 (s, IH), 3.91 (s, 2H), 3.90 (s, 3H), 3.79 (s, 3H).
  • 5
  • [ 949465-79-6 ]
  • [ 1011732-92-5 ]
YieldReaction ConditionsOperation in experiment
With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 0.5h; 4; 7 Carbonyldiimidazole (10.99 g) was slurried in 60 mL of THF at ambient temperature. Compound 4 (20 g) was added in one portion and the mixture was stirred at ambient temperature for 30 min to form a slurry of compound 5. In a separate flask 15.72 g of potassium monoethyl malonate was slurried in 100 mL of THF. Magnesium chloride (6.45 g) was added and the resulting slurry was warmed to 55 0C for 5 hours. The slurry of Compound 5 was transferred to the magnesium chloride/potassium monoethyl malonate mixture and stirred at 55 °C overnight. The mixture was then cooled to room temperature and quenched onto 120 mL of 28 wt% aqueous H3PO4. The phases were separated and the organic phase was washed successively with aqueous KHCO3 and NaCl solutions. The organic phase was concentrated to an oil and then coevaporated with ethanol. The resulting solid was dissolved in 100 mL ethanol and 12 rnL water. Compound 6a was crystallized by cooling. The solid was isolated by filtation and the product was washed with aqueous ethanol. After drying 21.74 g Compound 6a (89 % yield) was obtained: 1HNMR (DMSO-d6, 400 MHz) δ 7.51 (s, IH), 7.42-7.38 (m, IH), 7.12-7.10 (m, 2H), 6.70 (s, IH), 4.06 (q, J = 7.0 Hz, 2H), 3.89 (s, 8H), 3.81 (s, 2H), 1.15 (t, J = 7.0 Hz, 3H); Carbonyldiimidazole and imidazole are combined with anhydrous tetrahydrofuran. Compound 4 is added to this mixture to form Compound 5 and the reaction is monitored by HPLC. In a separate reactor potassium monoethylmalonate is combined with tetrahydrofuran before anhydrous magnesium chloride is added while maintaining the temperature NMT 30 °C. The resulting slurry is warmed to 50 °C and held for at least two hours before the Compound 5 mixture is added. The reaction is monitored by HPLC. Once the formation of Compound 5 is complete, the mixture is cooled to 18 to 25 0C and added to aqueous phosphoric acid to quench. The organic phase is washed with aqueous sodium bisulfate, brine, potassium bicarbonate and brine solutions before being polish filtered. The solvent is exchanged for anhydrous ethanol. Water is added and the mixture is warmed to dissolve solids, cooled to about 40 °C, seeded with Compound 6a and cooled to 0 to 5 °C. The product is filtered, washed with cold aqueous ethanol and dried at NMT 40 °C to yield Compound 6a.Procedure: 1. Charge 0.55 kg CDI and 0.042 kg imidazole to reactor 1.2. Charge 2.67 kg THF to reactor 1 and agitate to form a slurry.3. Charge 1.00 kg Compound 4 to reactor 1 in portions to moderate the CO2 offgas. This addition is endothermic4. Charge 0.89 kg KEM to reactor 2. 5. Charge 4.45 kg THF to reactor 2 and agitate to form a slurry.6. Charge 0.44 kg MgCl2 to reactor 2 (can be added in portions to moderate exotherm).7. Warm the contents of reactor 2 to 50 °C and agitate at that temperature for at least two hours. 8. Transfer the contents of reactor 1 to reactor 2. Mixture will become thick temporarily if transferred very rapidly.9. Agitate the contents of reactor 2 for at least 12 hours at 50 °C.10. Cool the slurry to ambient temperature.11. Quench the reaction by transferring the reaction mixture onto 7.0 kg of 28 wt% aqueous H3PO4 (2.3 kg 85 wt% H3PO4 dissolved in 4.7 kg H2O).This addition is exothermic. Final pH of aqueous layer should be 1-2. 12. Wash the organic (top) phase with 1.2 kg of 20 wt% aqueous NaHSO4 (0.24 kg OfNaHSO4 dissolved in 0.96 kg H2O). Final pH of aqueous layer should be 1-2.13. Wash the organic (top) phase with 1.2 kg of 20 wt% aqueous NaCl (0.24 kg of NaCl dissolved in 0.96 kg H2O)14. Wash the organic (top) phase with 5.0 kg of 10 wt% aqueous KHCO3 (0.50 kg OfKHCO3 dissolved in 4.5 kg H2O). Final pH of aqueous layer should be 8-10.15. Wash the organic (top) phase with 1.2 kg of 20 wt% aqueous NaCl (0.24 kg of NaCl dissolved in 0.96 kg H2O). Final pH of aqueous layer should be 7-9.16. Concentrate the organic phase and exchange the solvent to EtOH.17. Adjust the concentration to ~3.5 L/kginput.18. Charge 0.6 volumes of water. 19. Warm 70 - 80 0C to form a clear solution.20. Cool to 40 °C and seed with 0.1 wt% Compound 6.21. Cool slowly to 5 °C.22. Hold for at least 2 hours.23. Filter and wash the cake with two 1.35 kg volume portions of 50:50 EtOH:H2O (1.2 kg EtOH combined with 1.5 kg H2O).24. Dry the cake at less than 50 °C.
  • 6
  • [ 949465-79-6 ]
  • [ 85070-48-0 ]
  • [ 1011732-94-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoic acid With isopropylmagnesium chloride In tetrahydrofuran at 20 - 50℃; Stage #2: 2-fluoro-3-chlorobenzaldehyde In tetrahydrofuran at 20℃; 11 Compound 14 (5 g), isopropylmagnesium chloride (8.9 mL of 2M solution in THF) and THF (56 mL) were combined at ambient temperature and then warmed to 50 °C for ~5 hours. After cooling to ambient temperature and stirring overnight, 2.1 mL of 3-chloro-2-fluorobenzaldehyde was added drop wise to form a slurry. After stirring overnight the solid was isolated by filtration and washing with MTBE to yield compound 15a.
  • 7
  • [ 949465-78-5 ]
  • [ 949465-79-6 ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: methyl 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoate With sodium hydroxide; water; isopropyl alcohol at 70℃; for 3h; Stage #2: With hydrogenchloride; water In 3-methyl-butan-2-one at 10 - 20℃; 1.4 Step 4 Synthesis of 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoic acid Methyl 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoate was dissolved in isopropanol (20 mL), and 1 mol/L aqueous sodium hydroxide solution (30 mL) was added. The mixture was stirred at 70°C for 3 h, and completion of the reaction was confirmed by HPLC. After cooling the reaction mixture to room temperature, activated carbon (Sirasagi A) (1.0 g) was added. After stirring, the mixture was filtered using powder cellulose (KC FLOCK). The reaction container and the filter were washed with isopropanol (5 mL)/water (5 mL) solution, and combined with the filtrate. Water (20 mL) and hexane (20 mL) were added to the obtained filtrate and, after stirring, the organic layer was removed. The aqueous layer was washed again with hexane (20 mL). The aqueous layer was ice-cooled, methylisopropylketone (50 mL) was added while adding 2 mol/L hydrochloric acid solution (10 mL) dropwise at 10°C. After the addition, the mixture was stirred at room temperature and the aqueous layer was discarded. The organic layer was washed twice with 10% brine (20 mL). After washing, the solvent was evaporated under reduced pressure to give 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoic acid (4.8 g, yield 81%, from methyl 5-bromo-2,4-dimethoxybenzoate obtained in Step 2).
  • 8
  • [ 949465-79-6 ]
  • [ 536-74-3 ]
  • 1-(3-chloro-2-fluorobenzyl)-2,4-dimethoxy-5-(phenylethynyl)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With N-Bromosuccinimide; tetrakis(triphenylphosphine) palladium(0); caesium carbonate; 1,8-diazabicyclo[5.4.0]undec-7-ene; tricyclohexylphosphine In N,N-dimethyl-formamide at 120℃; for 24h; Schlenk technique; Glovebox; Inert atmosphere;
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 949465-79-6 ]

Fluorinated Building Blocks

Chemical Structure| 949465-87-6

[ 949465-87-6 ]

5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid

Similarity: 0.94

Chemical Structure| 1110663-19-8

[ 1110663-19-8 ]

1-(2-(Benzyloxy)-4-chloro-6-fluorophenyl)ethanone

Similarity: 0.85

Chemical Structure| 1805820-29-4

[ 1805820-29-4 ]

5-Chloro-2-ethoxy-4-fluorobenzoic acid

Similarity: 0.83

Chemical Structure| 1082042-25-8

[ 1082042-25-8 ]

4-Chloro-2-fluoro-6-methoxybenzoic acid

Similarity: 0.82

Chemical Structure| 1822668-12-1

[ 1822668-12-1 ]

1-(4-Chloro-2-fluoro-6-methoxyphenyl)ethanone

Similarity: 0.81

Aryls

Chemical Structure| 949465-87-6

[ 949465-87-6 ]

5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid

Similarity: 0.94

Chemical Structure| 1110663-19-8

[ 1110663-19-8 ]

1-(2-(Benzyloxy)-4-chloro-6-fluorophenyl)ethanone

Similarity: 0.85

Chemical Structure| 1805820-29-4

[ 1805820-29-4 ]

5-Chloro-2-ethoxy-4-fluorobenzoic acid

Similarity: 0.83

Chemical Structure| 1082042-25-8

[ 1082042-25-8 ]

4-Chloro-2-fluoro-6-methoxybenzoic acid

Similarity: 0.82

Chlorides

Chemical Structure| 949465-87-6

[ 949465-87-6 ]

5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid

Similarity: 0.94

Chemical Structure| 1110663-19-8

[ 1110663-19-8 ]

1-(2-(Benzyloxy)-4-chloro-6-fluorophenyl)ethanone

Similarity: 0.85

Chemical Structure| 1805820-29-4

[ 1805820-29-4 ]

5-Chloro-2-ethoxy-4-fluorobenzoic acid

Similarity: 0.83

Chemical Structure| 1082042-25-8

[ 1082042-25-8 ]

4-Chloro-2-fluoro-6-methoxybenzoic acid

Similarity: 0.82

Ethers

Chemical Structure| 949465-87-6

[ 949465-87-6 ]

5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid

Similarity: 0.94

Chemical Structure| 1110663-19-8

[ 1110663-19-8 ]

1-(2-(Benzyloxy)-4-chloro-6-fluorophenyl)ethanone

Similarity: 0.85

Chemical Structure| 1805820-29-4

[ 1805820-29-4 ]

5-Chloro-2-ethoxy-4-fluorobenzoic acid

Similarity: 0.83

Chemical Structure| 1082042-25-8

[ 1082042-25-8 ]

4-Chloro-2-fluoro-6-methoxybenzoic acid

Similarity: 0.82

Carboxylic Acids

Chemical Structure| 949465-87-6

[ 949465-87-6 ]

5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid

Similarity: 0.94

Chemical Structure| 1805820-29-4

[ 1805820-29-4 ]

5-Chloro-2-ethoxy-4-fluorobenzoic acid

Similarity: 0.83

Chemical Structure| 1082042-25-8

[ 1082042-25-8 ]

4-Chloro-2-fluoro-6-methoxybenzoic acid

Similarity: 0.82