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Chemical Structure| 677704-57-3 Chemical Structure| 677704-57-3

Structure of 677704-57-3

Chemical Structure| 677704-57-3

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Product Details of [ 677704-57-3 ]

CAS No. :677704-57-3
Formula : C12H11F3N2O
M.W : 256.22
SMILES Code : N#CC1=CC=C(N2CCOCC2)C(C(F)(F)F)=C1
MDL No. :MFCD11038561

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Application In Synthesis of [ 677704-57-3 ]

* 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 [ 677704-57-3 ]

[ 677704-57-3 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 110-91-8 ]
  • [ 67515-59-7 ]
  • [ 677704-57-3 ]
YieldReaction ConditionsOperation in experiment
95% at 60℃; for 8h; A mixture of 4-fluoro-3-trifluoro-methylbenzonitrile (Fluorochem 2223; 10 g; 52.8 mmol; 1 eq.) and morpholine (Fluka 69880; 9.25 ml 105.7 mmol; 2 eq.) was stirred at 600C for 8 hours. The mixture was cooled and diluted with water. The precipitate was filtered and dried to afford the title compound (12.9 g, 95%) as a white solid. HPLC (Method B) : Rt 3.61 min (purity 99.1 %). LC/MS : 257.1 (M+H)+. 1H NMR (CDCI3, 400MHz) delta 7.92 (1 H, s), 7.78-7.81 (1 H, d), 7.32-7.35 (1 H, d), 3.84-3.87 (4H, m), 3.04-3.06 (4H, m).
95% at 60℃; for 8h; A mixture of 4-fluoro-3-trifluro-methylbenzonitrile (Fluorochem2223, 10 g, 52.8 mmol) and morpholine (9.25ml_, 105.7 mmol) was heated at 6O C under N2 for 8 hours. The mixture was cooled and diluted with water (100 ml_). The precipitate was filtered affording the title compound as a white solid (12.9 g, 95%). 1H NMR (CDCI3, 400 MHz) delta 7.92 (s, 1 H), 7.78- 7.81 (d, 1 H), 7.32-7.35 (d, 1 H), 3.84-3.87 (m, 4H), 3.04-3.06 (m, 4H). LC/MS (Method A): 257.1 (M+H)+. HPLC (Method B) Rt 3.61 min (Purity: 99.1%).
85% In dimethyl sulfoxide; at 90℃; for 18h; Preparation No.11: 4-morpholino-3-(trifluoromethyl)benzonitrile; To a solution of <strong>[67515-59-7]4-fluoro-3-(trifluoromethyl)benzonitrile</strong> (15 g, 79 mmol) in dimethylsulfoxide (160 mL) was added morpholine (13.8 mL, 159 mmol) and potassium carbonate (16.4 g, 119 mmol). The mixture was heated at about 900C for 18 hours. The mixture was cooled to ambient temperature and the solid was removed by filtration. The fitrate was partitioned between ethyl acetate (1.8 L) and water (1.5 L). The organic layer was washed with water (1.0 L) and brine (1.0 L) and dried over anhydrous magnesium sulphate. The solvent was removed in vacuo to give 4-morpholino-3-(trifluoromethyl)benzonitrile (17.25 g, 85 %). 1H NMR (DMSO-lambda6, 400MHz) delta 8.18 (d, J = 2.05 Hz, IH), 8.09 (dd, J = 8.51, 2.06 Hz, IH), 7.60 (d, J = 8.52 Hz, IH), 3.69-3.75 (m, 4H), 2.97-3.04 (m, 4H).
85% With potassium carbonate; In dimethyl sulfoxide; at 90℃; for 18h; Preparation No.16: 4-morpholino-3-(trifluoromethyl)benzonitrile; To a solution of <strong>[67515-59-7]4-fluoro-3-(trifluoromethyl)benzonitrile</strong> (15 g, 79 mmol) in dimethylsulfoxide (160 mL) was added morpholine (13.8 mL, 159 mmol) and potassium carbonate (16.4 g, 1 19 mmol). The mixture was heated at about 90 C for about 18 h. The mixture was cooled to ambient temperature and the solid was removed by filtration. The filtrate was partitioned between ethyl acetate (1.8 L) and water (1.5 L). The organic layer was washed with water (1.0 L) and brine (1.0 L) and dried over anhydrous magnesium sulphate. The solvent was removed in vacuo to give 4-morpholino-3-(trifluoromethyl)benzonitrile (17.25 g, 85 %). .H NMR (DMSO-J6, 400MHz) delta ppm 8.18 (d, J = 2.05 Hz, 1H), 8.09 (dd, J = 8.51 , 2.06 Hz, 1H), 7.60 (d, J = 8.52 Hz, 1H), 3.69-3.75 (m, 4H), 2.97-3.04 (m, 4H).
80% With potassium carbonate; In dimethyl sulfoxide; at 90℃; K2CO3 (2.0 eq.) and 2.0 equiv. of the corresponding nucleophile (Nu in scheme 16) were added to a solution of <strong>[67515-59-7]4-fluoro-3-(trifluoromethyl)benzonitrile</strong> (1.0 eq.) in DMSO. The mixture was heated at 90 0C overnight. The mixture was cooled to r.t. and the solids were removed by filtration. Water was added to the filtrate and the product was precipitated, collected by filtration, washed with water and dried under vacuum.The following substances were synthesized following general procedure D for the nucleophilic aromatic substitution of <strong>[67515-59-7]4-fluoro-3-(trifluoromethyl)-benzonitrile</strong>. The solvent system used for the purification, the yield and analytical data is given for each compound. Yield: 80%1H NMR (CDCl3) delta 7.92 (d, IH), 7.79 (m, IH), 7.33 (d, IH), 3.86 (m, 4H), 3.95 (m, 4H)
80% With potassium carbonate; In dimethyl sulfoxide; at 90℃; General Procedure D for the Nucleophilic Aromatic Substitution of <strong>[67515-59-7]4-fluoro-3-(trifluoromethyl)-benzonitrile</strong> (see Scheme 16 Above).K2CO3 (2.0 eq.) and 2.0 equiv. of the corresponding nucleophile (Nu in scheme 16) were added to a solution of <strong>[67515-59-7]4-fluoro-3-(trifluoromethyl)benzonitrile</strong> (1.0 eq.) in DMSO. The mixture was heated at 90 C. overnight. The mixture was cooled to r.t. and the solids were removed by filtration. Water was added to the filtrate and the product was precipitated, collected by filtration, washed with water and dried under vacuum.The following substances were synthesized following general procedure D for the nucleophilic aromatic substitution of <strong>[67515-59-7]4-fluoro-3-(trifluoromethyl)-benzonitrile</strong>. The solvent system used for the purification, the yield and analytical data is given for each compound.4-Morpholino-3-(trifluoromethyl)benzonitrileYield: 80% 1H NMR (CDCl3) delta 7.92 (d, 1H), 7.79 (m, 1H), 7.33 (d, 1H), 3.86 (m, 4H), 3.95 (m, 4H)
In ISOPROPYLAMIDE; at 145℃; for 19h; <strong>[67515-59-7]4-Fluoro-3-(trifluoromethyl)benzonitrile</strong> (2.0g, 10.58mmol) was dissolved in dimethyl acetamide (35mL), morpholine (2.88mL, 31.73mmol) was added thereto, and the mixture was subjected to a reaction at 145C for 19 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50mL), and the organic layer was washed with an aqueous sodium hydrogen carbonate solution (50mL). The organic layer was washed with water, dried with sodium sulfate, and the solvent was distilled under reduced pressure. The concentrated mixture was crystallized with ethyl acetate (lOmL) and n-hexane (80mL) to obtain the title compound as a brown solid (2.1g).1H NMR (DMSO-d6) delta 8.17 (s, 1H), 8.08 (d, 1H), 7.58 (d, 1H), 3.71 (m, 4H), 2.99 (m, 4H).
2.1 g In N,N-dimethyl acetamide; at 145℃; for 19h; <strong>[67515-59-7]4-Fluoro-3-(trifluoromethyl)benzonitrile</strong> (2.0 g, 10.58 mmol) was dissolved in dimethyl acetamide (35 mL), morpholine (2.88 mL, 31.73 mmol) was added thereto, and the mixture was subjected to a reaction at 145 C. for 19 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL), and the organic layer was washed with an aqueous sodium hydrogen carbonate solution (50 mL). The organic layer was washed with water, dried with sodium sulfate, and the solvent was distilled under reduced pressure. The concentrated mixture was crystallized with ethyl acetate (10 mL) and n-hexane (80 mL) to obtain the title compound as a brown solid (2.1 g). 1H NMR (DMSO-d6) delta 8.17 (s, 1H), 8.08 (d, 1H), 7.58 (d, 1H), 3.71 (m, 4H), 2.99 (m, 4H).

 

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