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CAS No. : | 1877-72-1 | MDL No. : | MFCD00002486 |
Formula : | C8H5NO2 | Boiling Point : | - |
Linear Structure Formula : | (NC)(C6H4)COOH | InChI Key : | GYLKKXHEIIFTJH-UHFFFAOYSA-N |
M.W : | 147.13 | Pubchem ID : | 15875 |
Synonyms : |
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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: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sulfuric acid; for 12h;Reflux; | To a stirred solution of 3-cyanobenzoic acid (XXVII; 6 g; 41 mmol) in methanol (80 mL) was added catalytic sulfuric acid (5 mL). The reaction mixture was heated to a reflux for 12 hours. The reaction mixture was cooled, concentrated under reduced pressure and diluted with water.The aqueous layer was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with sodium bicarbonate, brine, dried over Na2SO4, filtered and concentrated under vacuum to afford methyl 3-cyanobenzoate as a white solid (XXVIII; 3 g, 62percent yield). ?H NMR (400 MHz, CDC13): oe 8.36 (s, 1H), 8.26-8.24 (d, J = 8.0 Hz, 1H), 7.84-7.82 (d, J = 8.0 Hz, 1H), 7.63-7.58 (m 1H), 3.95 (s, 3H). |
Preparation H11: Synthesis of 3-(thiazol-2-yl)benzoic Acid Preparation H11, Step 1: 10 g (0.068 mol) of 3-cyano benzoic acid was taken in 150 ml of dry dichloromethane and cooled to 0° C. Added 50 ml of oxalyl chloride drop wise followed by 5 drops of dry DMF. The reaction mixture was stirred at RT overnight. Dichloromethane was removed and dry methanol (50 ml) was added and stirred at rt for 2 h. Excess methanol was removed and the residue was dissolved in ethyl acetate. The ethyl acetate layer was washed with 10percent of sodium bicarbonate, brine and concentrated to give methyl 3-cyanobenzoate (7 g) as a white solid. | ||
11.5 g | With sulfuric acid; In toluene; at 70 - 100℃; for 5h; | 10.0 g (0.068 mol) of 3-cyanobenzoic acid, 20 ml of toluene, 20 g (0.625 mol) of methanol and 0.4 g (0.004 mol) of concentrated sulfuric acid were placed in a reaction vessel and stirred for 5 hours while dehydrating at an internal temperature of 70 to 100 ° C. . The reaction solution was cooled and water was added to separate the solution. The organic layer was concentrated under reduced pressure to obtain 11.5 g of a white solid. Next, the whole amount of the obtained white solid was placed in a reaction vessel and dissolved in 40 ml of methanol, and 5.3 g (0.076 mol) of hydroxylamine hydrochloride was added thereto. 8.1 g (0.078 mol) of triethylamine was added and the mixture was stirred at 30 to 40 ° C. for 2 hours. The reaction solution was cooled, 8.1 g (0.079 mol) of acetic anhydride was added, and the mixture was further stirred for 30 minutes. After completion of the reaction, the reaction solution was cooled and placed in a pressure-resistant container, 0.67 g of 10percent palladium carbon catalyst and 0.34 g of water were added and reacted under a hydrogen pressure of 0.3 Mpa for 4 hours. The catalyst was separated by filtration and washed with methanol to obtain the desired methanol solution. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | 13A Methyl 3-cyanobenzoate Following the process described in example 9 (point A), starting from 3-cyanobenzoic acid, the title compound was prepared as a yellowish oil (80percent yield). 1H N.M.R. (300 MHz, CDCl3) delta ppm: 3.93 (s, 3H); 7.56 (t, 1H); 7.81 (dd, 1H); 8.23 (dd, 1H); 8.29 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 0.5h; | To a solution of 3-Cyanobenzoic acid (44.14 g, 300 mmol) in DMF (0.6 L) was added K2CO3 (62.19 g, 450 mmol) and then stirred for 30 min at room temperature. To the suspension was added methyl iodide (28 mL, 450 mmol) over 20 min, and the reaction mixture was stirred further 4 h at room temperature. The reaction mixture was poured to 1.2 L of ice water and stirred for 30 min, and the precipitate was filtered off. The white cake was dissolved in methanol (70 mL), and then re-precipitated in cold water. The desired product was obtained as a white powder with 79percent yield (38 g, 99percent purity by LC/UV). 1H-NMR (CDCl3) delta 8.85 (2H), 8.28 (1H), 8.02 (1H), 4.17 (3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In methanol; hexane; toluene; at 20℃; for 1.5h; | Example 47AMethyl 3-cyanobenzoate; 100 mg (0.68 mmol) of 3-cyanobenzoic acid are initially charged in 4 ml of toluene and 3.5 ml of methanol, and 0.51 ml (1.02 mnmol) of a 2 M solution of trimethylsilyldiazomethane in n-hexane is added at RT. The reaction mixture is stirred at RT for 1.5 h. After removal of the solvent on a rotary evaporator the residue is dried under reduced pressure. The product is obtained in pure form and is directly reacted further.Yield: 116 mg (100percent of theory)LC-MS (Method 4): Rt=1.93 min; MS (ESIpos): m/z=162 [M+H]+. |
62% | To a solution of 3-cyanobenzoic acid (7.35 g, 50 mmol) in DCM/ MeOH (80 ml/ 20 ml) is added trimethylsilyldiazomethane (2M solution in ether; 1 eq, 50 mmol) and the mixture is stirred for 1 h. Acetic acid is added dropwise until the yellow colour disappeared. The solvents are then removed in vacuo. The residue is dissolved in DCM and washed with water. The organic phase is dried (MgSO4) and concentrated in vacuo to give the title compound (5 g, 62percent) LC/MS: 93percent MH+, m/z not ionised, Rt = 1.14 mins. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1 Synthesis of N-[2-(3-cyanophenoxy)ethyl]-3-cyanobenzamide: The title compound was obtained from 162 mg (1.1 mmol) of 3-cyanobenzoic acid and 163 mg (1.0 mmol) of <strong>[120351-94-2]3-(2-aminoethoxy)benzonitrile</strong> in the same manner as that of step 4 in Example 1. Yield: 251 mg (0.86 mmol) (86 %) H-NMR (CDCl3) delta 3.92 (2H, dt), 4.19 (2H, t), 6.67 (1H, br), 7.16 (1H, d),7.18 (1H, s), 7.28 (1H, d), 7.40 (1H, t), 7.59 (1H, t), 7.80 (1H, t), 7.80 (1H, d), 8.03 (1H, d), 8.09 (1H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | To a solution of 3-Cyanobenzoic acid (44.14g, 300mmol) in DMF (0.6 L) was added K2CO3 (62.19g, 450mmol) and then stirred for 30 min at room temperature. To the suspension was added methyl iodide (28 mL, 450 mmol) over 20 min, and the reaction mixture was stirred further 4h at room temperature. The reaction mixture was poured to 1.2L of ice water and stirred for 30 min, and the precipitate was filtered off. The white cake was dissolved in methanol (70 mL), and then re-precipitated in cold water. The desired product was obtained as a white powder with 79percent yield (38g, 99percent purity by LC/UV). 1H-NMR (CDCl3) delta 8.85 (2H), 8.28 (IH), 8.02 (IH), 4.17 (3H). | |
79% | To 44.14 g of 3-cyanobenzoic acid dissolved in 0.6 liter of DMF was added 62. 19 g of potassium carbonate,And the mixture was stirred at room temperature for 30 minutes. To the suspension was added 28 ml (450 mmol) of methyl iodide over 20 minutes,The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was poured into 1. 2 liters of ice water, stirred for 30 minutes, and the precipitate was filtered off. The white cake was dissolved in 70 ml of methanol and then reprecipitated in cold water.To give methyl 3-cyanobenzoic acid in a yield of 79percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | A solution of 3-cyanobenzoic acid (1.58 g, 0.01 mol), HOBT (3.03 g, 0.02 mol), EDCI (3.8 g, 0.02 mol), DIEA (2.5 g, 0.02 mol) in DCM (200 mL) was stirred at RT for 15 min. tert-Butyl 3-amino-4-hydroxypyrrolidine-l-carboxylate (2.3 g, 0.01 mol) was added, and the mixture was stirred at RT overnight. The reaction was diluted with DCM, washed with H2O, and dried over Na2SO4. Purification by silica gel chromatography (PE : EtOAc gradient = 8:1 to 2:1) afforded the product tert-butyl 3-(3- cyanobenzamido)-4-hydroxypyrrolidine-l-carboxylate (2 g, 62%) as a white solid. The product was carried directly to the next step. |
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