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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Cyclohexanecarboxylic acid is a Valproate structural analogue with anticonvulsant action.
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CAS No. : | 98-89-5 |
Formula : | C7H12O2 |
M.W : | 128.17 |
SMILES Code : | O=C(C1CCCCC1)O |
MDL No. : | MFCD00001461 |
InChI Key : | NZNMSOFKMUBTKW-UHFFFAOYSA-N |
Pubchem ID : | 7413 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With pyridine; In diethyl ether; for 10h; | To an ether solution (5 mL) of cyclohexanecarboxylic acid (250 mg, 1.95 mmol) was added pyridine (0.5 mL) and cyclohexanecarbonyl chloride (286 mg, 0.261 mL, 1.95 MMOL). After 10 h, the suspension was diluted with ether (20 mL), washed with ice-cold 5% HCl solution (1x50 mL) and concentrated NaHCO3 solution (1x50 mL) and dried over Na2S04. All solvent was removed in vacua to give 350 mg of cyclohexanecarboxylic anhydride as A colorless oil. A portion of the cyclohexanecarboxylic anhydride. (226 mg, 0. 948 mmol) was added to a sodium carbonate solution (1 M, 2 mL) of the aminophosphate 21a (110 mg, 0.412 mmol). After 15 h, it was acidified to PH#1 by addition of concentrated HCI solution at 0 C. Preparative HPLC purification afforded 50 mg (36% yield) of the title compound 25-17. 1H NMR (CD3OD) : δ 7. 27-7. 1 (5H, m), 6.67 (1H, br d), 4.34 (1H, br s), 4.08 (1H, m), 3.96 (1H, m), 2.90 (1H, dd, J=14.4, 6.6 Hz), 2. 78 (1H, dd, J=14.9, 9 Hz), 2.10 (1H, br t), 1.79-1. 51 (5H, m), 1. 33-1. 02 (5H, m); LCMS (ESP): 342 (M+H+) ; 340 (M-H)-. | |
With pyridine; In diethyl ether; for 10h; | Example 25-17 Phosphoric acid mono-{2-[(1-cyclohexyl-methanoyl)-amino]-3-phenyl-propyl}ester To an ether solution (5 mL) of cyclohexanecarboxylic acid (250 mg, 1.95 mmol) was added pyridine (0.5 mL) and cyclohexanecarbonyl chloride (286 mg, 0.261 mL, 1.95 mmol). After 10 h, the suspension was diluted with ether (20 mL), washed with ice-cold 5% HCl solution (1*50 mL) and concentrated NaHCO3 solution (1*50 mL) and dried over Na2SO4. All solvent was removed in vacuo to give 350 mg of cyclohexanecarboxylic anhydride as a colorless oil. | |
General procedure: To a flamed-dried flask with magnetic stir bar, was added aliphatic acid (1.0 equiv), dried DCM (1.0 M) and triethylamine (1.05 equiv) successively. The solution was stirred for 30 minutes at 0 0C. Then acyl chloride (1.05 equiv) was added dropwise to the mixture and stirred overnight at rt. The solvent was evaporated by vacuum to afford the crude mixture. And the mixture was dissolved in n-hexane. Then the residue was filtered through a small plug of celite and concentrated to afford the anhydrides. This product was used to next catalytic reaction without any further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With magnesium basic carbonate; di-tert-butyl dicarbonate; at 25℃; for 6h; | Examples 1420 In each example, methacrylic acid anhydride was produced under conditions the same as in Example 1 except that methacrylic acid was replaced with the type of carboxylic acid (6.0 mmol) shown in Table 1, and the amount of magnesium carbonate hydroxide relative to di-t-butyl dicarbonate was changed to 4 mol % or 8 mol %, while the rest of the conditions were set to be the same as in Example 1. The reaction results obtained 412 hours after the start of reactions are shown in Table 1. |
90% | General procedure: A few drops of water were added to the mixture of carboxylic acid (1 mmol) and K2CO3 (1.5 mmol, 0.20 g) and put in MW for 2-4 min (900 W), then dry CH3CN (5 mL) and TsCl (0.5 mmol, 0.10 g) were added. The reaction mixture was allowed to ultrasound irradiation for suitable time. After the completion of the reaction, CH2Cl2 or Et2O(2×10 mL) was added to the reaction mixture, stirred, filtered, and the organic layer was dried over CaCl2. The evaporation of the solvent afforded a highly pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃; for 4h; | EXAMPLE 15: Preparation of (Z)-7V-(6-(cyclohexanecarbonyloxyamino)-6- oxohexyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-lH- pyrrole-3-carboxamide (Compound 21)Cyclohexanecarboxylic anhydride (5 mL) and cyclohexanecarboxylic acid (150 mg, 1.17 mmol) was added to a solution of compound 4 (500 mg, 1.17 mmol) in <n="68"/>THF (120ml) and DMF (5 mL). The solution was stirred at room temperature for 4 h. THF was removed in vacuo, and then water (100 mL) was added. The mixture was adjusted to pH 7-8 with saturated aqueous NaHCθ3. The resulting solid was collected by filtration, washed with water for three times, dried and purified by preparative HPLC to give product 21 as a yellow solid (100 mg, 13%). LCMS: 539 [M+l]+, 1H NMR (DMSO-(Z6): δ 1.32 (m, 7H), 1.53 (m, 5H), 1.66 (m, 2H), 1.85 (m, 2H), 2.11 (t, J= 6.45 Hz, 2H), 2.39 (s, 3H), 2.41 (s,3H), 3.20 (m, 2H), 6.85 (m,2H), 7.71 (m, 3H) , 10.89 (s, IH), 11.54 (s, 1H),13.67 (s, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N?,N?-tetramethyl-N?-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate; In 1,4-dioxane; at 20℃; for 1h;Inert atmosphere; Irradiation; | General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1-3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5-10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C-N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N?,N?-tetramethyl-N?-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate; In 1,4-dioxane; at 20℃; for 1h;Inert atmosphere; Irradiation; | General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1?3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5?10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C?N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N?,N?-tetramethyl-N?-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate; In 1,4-dioxane; at 20℃; for 1h;Inert atmosphere; Irradiation; | General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1?3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5?10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C?N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N?,N?-tetramethyl-N?-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate; In 1,4-dioxane; at 20℃; for 1h;Inert atmosphere; Irradiation; | General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1?3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5?10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C?N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used. |
Tags: Cyclohexanecarboxylic acid | Carboxylic Acids | Aliphatic Cyclic Hydrocarbons | Organic Building Blocks | 98-89-5
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