* 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.
Imidazole is added to the reactor (3.75g, 55 . 0mmol), thf (50.0 ml), the reaction is cooled to 0 °C, the ethyl chloroformate (2.58 ml, 27 . 0mmol) dropwise wherein the 0 °C stirring 1h rear, moving to the room temperature, reaction 4h. Filtering the reaction liquid, turns on lathe does, its re-dissolved in 100 ml diethyl ether, washed with water, drying by anhydrous magnesium sulphate the organic phase, the turns on lathe does colorless liquid, i.e. compound 3 (1.28g, 17percent yield)
17%
at 0 - 20℃; for 5 h;
Imidazole is added to the reactor (3.75g, 55 . 0mmol), thf (50.0 ml), the reaction is cooled to 0 °C, the ethyl chloroformate (2.58 ml, 27 . 0mmol) dropwise wherein the 0 °C stirring 1h rear, moving to the room temperature, reaction 4h. Filtering the reaction liquid, turns on lathe does, its re-dissolved in 100 ml diethyl ether, washed with water, drying by anhydrous magnesium sulphate the organic phase, the turns on lathe does colorless liquid, i.e. compound 3 (1.28g, 17percent yield);
Reference：
[1] Angewandte Chemie - International Edition, 2012, vol. 51, # 33, p. 8304 - 8308
[2] Organic Letters, 2010, vol. 12, # 20, p. 4572 - 4575
[3] Patent: CN105566347, 2016, A, . Location in patent: Paragraph 0033; 0034; 0035
[4] Patent: CN105503932, 2016, A, . Location in patent: Paragraph 0045; 0046; 0047
[5] Justus Liebigs Annalen der Chemie, 1957, vol. 609, p. 75,82
[6] Tetrahedron Letters, 1982, vol. 23, # 20, p. 2113 - 2116
[7] Journal of Organic Chemistry, 1982, vol. 47, # 21, p. 4040 - 4045
[8] Tetrahedron, 2011, vol. 67, # 46, p. 8851 - 8859
[9] Tetrahedron Letters, 2012, vol. 53, # 9, p. 1060 - 1062
3
[ 64-17-5 ]
[ 530-62-1 ]
[ 19213-72-0 ]
Reference：
[1] Nucleosides and Nucleotides, 1999, vol. 18, # 9, p. 2109 - 2120
[2] Tetrahedron Letters, 1982, vol. 23, # 20, p. 2113 - 2116
[3] Gazzetta Chimica Italiana, 1993, vol. 123, # 10, p. 559 - 562
[4] Green Chemistry, 2012, vol. 14, # 2, p. 326 - 329
[5] Tetrahedron Letters, 2012, vol. 53, # 19, p. 2373 - 2376
4
[ 288-32-4 ]
[ 63436-79-3 ]
[ 19213-72-0 ]
Reference：
[1] Journal of Organic Chemistry, 1980, vol. 45, # 22, p. 4519 - 4522
5
[ 288-32-4 ]
[ 74877-64-8 ]
[ 19213-72-0 ]
Reference：
[1] Journal of Organic Chemistry, 1980, vol. 45, # 22, p. 4519 - 4522
6
[ 64-17-5 ]
[ 530-62-1 ]
[ 288-32-4 ]
[ 19213-72-0 ]
Reference：
[1] Synthetic Communications, 2000, vol. 30, # 1, p. 23 - 30
[2] Russian Journal of Applied Chemistry, 2012, vol. 85, # 3, p. 456 - 459
7
[ 110-85-0 ]
[ 19213-72-0 ]
[ 142-64-3 ]
[ 120-43-4 ]
Reference：
[1] Green Chemistry, 2012, vol. 14, # 2, p. 326 - 329
General procedure: Carboxylic acid (0.5 mmol) and MImC (2a, 1.0 mmol) were placed in a dry 20 mL vial with a Teflon tape-coated thread. A magnetic stirbar was added, followed by dry MeCN (1.0 mL), and the vial was quickly sealed with a plastic cap (gas is evolved during the course of the reaction. All experiments should be performed behind a blast shield if a sealed container is used.). The reaction mixture was then stirred at 23 °C for 15 min and then heated to 80 °C using a heating block for 24 h. The mixture was cooled to room temperature and then the vial was carefully opened (CAUTION: vial under pressure.). The volatiles were removed in vacuo, the resulting residue was dissolved in diethyl ether (20 mL), and then washed with 1 M HCl (10 mL). The aqueous layer was back-extracted with diethyl ether (20 mL) and the organic fractions were combined, washed with a saturated solution of NaHCO3 and then brine, dried over MgSO4, and concentrated in vacuo to afford the desired ester.
Stage #1: With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5 h; Stage #2: at -78 - 20℃;
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 °C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 °C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4percent ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81percent yield) as a colorless liquid.
Imidazole is added to the reactor (3.75g, 55 . 0mmol), thf (50.0 ml), the reaction is cooled to 0 C, the ethyl chloroformate (2.58 ml, 27 . 0mmol) dropwise wherein the 0 C stirring 1h rear, moving to the room temperature, reaction 4h. Filtering the reaction liquid, turns on lathe does, its re-dissolved in 100 ml diethyl ether, washed with water, drying by anhydrous magnesium sulphate the organic phase, the turns on lathe does colorless liquid, i.e. compound 3 (1.28g, 17% yield)
17%
In tetrahydrofuran; at 0 - 20℃; for 5h;
Imidazole is added to the reactor (3.75g, 55 . 0mmol), thf (50.0 ml), the reaction is cooled to 0 C, the ethyl chloroformate (2.58 ml, 27 . 0mmol) dropwise wherein the 0 C stirring 1h rear, moving to the room temperature, reaction 4h. Filtering the reaction liquid, turns on lathe does, its re-dissolved in 100 ml diethyl ether, washed with water, drying by anhydrous magnesium sulphate the organic phase, the turns on lathe does colorless liquid, i.e. compound 3 (1.28g, 17% yield);
From this compound can be obtained 4(5)-chloro-2-(ethoxycarbonyl)-5(4)-phenylimidazole having a melting point of 133 to 135 C. in the same manner as in Step [3] of Synthesis Example 1, from which 2-carbamoyl-4(5)-chloro-5(4)-phenylimidazole (Compound No. 6) having a melting point of 275 to 277 C. can further be obtained in the same manner as in Step [4] of Synthesis Example 1.
17
[ 19213-72-0 ]
[ 16042-25-4 ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydroxide;
SYNTHESIS EXAMPLE 9 Synthesis of 4(5)-Chloro-5(4)-phenylimidazole-2-carboxylic acid (Compound No. 15) 2.5 g of 4(5)-chloro-2-(ethoxycarbonyl)-5(4)-phenylimidazole (Compound No. 5) was added to 50 ml of a 5% aqueous sodium hydroxide solution, and the mixture was reacted at the reflux temperature for one hour to obtain a reaction mixture including sodium 4(5)-chloro-5(4)-phenylimidazole-2-carboxylate. The reaction mixture was poured into ice water and neutralized with hydrochloric acid. A precipitated crystal was separated by filtration and washed with water to obtain 4(5)-chloro-5(4)-phenylimidazole-2-carboxylic acid (Compound No. 15) having a melting point of 158 to 160 C.
EXAMPLE 4 1.4 g of <strong>[19213-72-0]1-ethoxycarbonylimidazole</strong>, 2.5 g of ethyl 4-chloromethylphenoxyacetate and 1.7 g of sodium iodide were added to 5 ml of dry acetonitrile, and the mixture was stirred at room temperature for 6 hours. After completion of the reaction, the insoluble materials were filtered off and the filtrate was concentrated under reduced pressure. The residue was triturated with an adequate amount of dry diethyl ether, the resulting powder was collected by filtration and dried to obtain 4.6 g of 1-ethoxycarbonyl-3-(4-ethoxycarbonylmethoxybenzyl)imidazolium iodide (quantitative yield). Colorless hygroscopic amorphous. IR absorption spectrum (KBr) nuCO: 1795, 1750 cm-1 NMR spectrum (d6 -DMSO) delta: 1.13(t, 3H, J=7 Hz), 1.35(t, 3H, J=7 Hz), 4.15 (q, 2H, J=7 Hz), 4.53(q, 2H, J=7 Hz), 4.77(s, 2H), 5.48(s, 2H), 6.96(d, 2H, J=8 Hz), 7.49(d, 2H, J=8 Hz), 7.94(m, 1H), 8.10(m, 1H), 10.09(m, 1H).
1-ethoxycarbonyl-3-[4-(2-methoxycarbonylvinyl)benzyl]imidazolium bromide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In acetonitrile;
EXAMPLE 3 To 5 ml of dry acetonitrile were added 1.4 g of <strong>[19213-72-0]1-ethoxycarbonylimidazole</strong> and 2.55 g of methyl 4-bromomethylcinnamate, the mixture was stirred for 5 hours at room temperature. The precipitated crystals were collected by filtration and recrystallized from acetonitrile/diethyl ether to yield 2.9 g of 1-ethoxycarbonyl-3-[4-(2-methoxycarbonylvinyl)benzyl]imidazolium bromide. Melting Point: 129 C. (decomposition). IR-absorption spectra (KBr): nuCO: 1785 cm-1, 1715 cm-1. NMR spectra (d6 -DMSO): delta: 1.35(t, 3H, J=7 Hz), 3.70(s, 3H), 4.53(q, 2H, J=7 Hz), 5.60(s, 2H), 7.47-8.00(m, 5H), 8.10(m, 1H), 8.25(m, 1H), 8.65(d, 1H, J=16 Hz), 10.27(m, 1H). Elementary analysis as C17 H19 O4 N2 Br:
EXAMPLE 13 To a solution of 3.0 g of 2-(m-nitroaniline)-N-cyclopropylmethylbenzamide and 25 ml of dry tetrahydrofuran was added 1.0 g of approximately 55 % sodium hydride, and stirring was then performed for 30 minutes at room temperature. To this was added dropwise 4.2 g of <strong>[19213-72-0]1-ethoxycarbonylimidazole</strong> and the mixture was refluxed for 3 hours. After the reaction was complete, the solvent was evaporated from the resulting mixture under reduced pressure, and to the residue obtained was added water to yield a precipitate. This product was recrystallized from methanol to yield 2.6 g of 1-(m-nitrophenyl)- 3-cyclopropylmethylquinazoline-2,4(1H, 3H)-dione as colorless needles, melting at 163-164 C. Analysis-Calculated for C18 H15 N3 O4: C, 64.09; H, 4.49; N, 12.46. Found: C, 63.86; H, 4.52; N, 12.57.
In [D3]acetonitrile; at 80℃; for 24h;Inert atmosphere; Sealed vial;
General procedure: Imidazole carbamate (2 equiv) and phenol (1 equiv) were dissolved in CD3CN to make a 0.5 M solution with respect to phenol in a 4 mL screwcap vial. The vial was then sealed and the mixture was heated to 80 C for 24 h. The reaction mixture was cooled and an aliquot was removed and analyzed by 1H NMR.
In N,N-dimethyl-formamide; at 80℃; for 24h;Inert atmosphere; Sealed vial;
General procedure: Carboxylic acid (0.5 mmol) and MImC (2a, 1.0 mmol) were placed in a dry 20 mL vial with a Teflon tape-coated thread. A magnetic stirbar was added, followed by dry MeCN (1.0 mL), and the vial was quickly sealed with a plastic cap (gas is evolved during the course of the reaction. All experiments should be performed behind a blast shield if a sealed container is used.). The reaction mixture was then stirred at 23 C for 15 min and then heated to 80 C using a heating block for 24 h. The mixture was cooled to room temperature and then the vial was carefully opened (CAUTION: vial under pressure.). The volatiles were removed in vacuo, the resulting residue was dissolved in diethyl ether (20 mL), and then washed with 1 M HCl (10 mL). The aqueous layer was back-extracted with diethyl ether (20 mL) and the organic fractions were combined, washed with a saturated solution of NaHCO3 and then brine, dried over MgSO4, and concentrated in vacuo to afford the desired ester.
In acetonitrile; at 80℃; for 24h;Inert atmosphere; Sealed vial;
General procedure: Carboxylic acid (0.5 mmol) and MImC (2a, 1.0 mmol) were placed in a dry 20 mL vial with a Teflon tape-coated thread. A magnetic stirbar was added, followed by dry MeCN (1.0 mL), and the vial was quickly sealed with a plastic cap (gas is evolved during the course of the reaction. All experiments should be performed behind a blast shield if a sealed container is used.). The reaction mixture was then stirred at 23 C for 15 min and then heated to 80 C using a heating block for 24 h. The mixture was cooled to room temperature and then the vial was carefully opened (CAUTION: vial under pressure.). The volatiles were removed in vacuo, the resulting residue was dissolved in diethyl ether (20 mL), and then washed with 1 M HCl (10 mL). The aqueous layer was back-extracted with diethyl ether (20 mL) and the organic fractions were combined, washed with a saturated solution of NaHCO3 and then brine, dried over MgSO4, and concentrated in vacuo to afford the desired ester.
In acetonitrile; at 80℃; for 24h;Inert atmosphere; Sealed vial;
General procedure: Carboxylic acid (0.5 mmol) and MImC (2a, 1.0 mmol) were placed in a dry 20 mL vial with a Teflon tape-coated thread. A magnetic stirbar was added, followed by dry MeCN (1.0 mL), and the vial was quickly sealed with a plastic cap (gas is evolved during the course of the reaction. All experiments should be performed behind a blast shield if a sealed container is used.). The reaction mixture was then stirred at 23 C for 15 min and then heated to 80 C using a heating block for 24 h. The mixture was cooled to room temperature and then the vial was carefully opened (CAUTION: vial under pressure.). The volatiles were removed in vacuo, the resulting residue was dissolved in diethyl ether (20 mL), and then washed with 1 M HCl (10 mL). The aqueous layer was back-extracted with diethyl ether (20 mL) and the organic fractions were combined, washed with a saturated solution of NaHCO3 and then brine, dried over MgSO4, and concentrated in vacuo to afford the desired ester.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
ethyl 2-(2-chloro-6-fluorophenyl)acetate[ No CAS ]
[ 190521-88-1 ]
Yield
Reaction Conditions
Operation in experiment
75%
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of compound 4a (700 mg, 5.18 mmol) in THF (10 mL) was added LiHMDS (6.2 ml, 1 M sol. in THF, 6.2 mmol) at 0 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (870 mg, 6.22 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at 0 C and stirred at rt for 4 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 10% ethyl acetate/pet ether gave the pure compound 5a (720 mg, 68% yield) as a colorless liquid.
To a stirred solution of compound 4a (700 mg, 5.18 mmol) in THF (10 mL) was added LiHMDS (6.2 ml, 1 M sol. in THF, 6.2 mmol) at 0 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (870 mg, 6.22 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at 0 C and stirred at rt for 4 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 10% ethyl acetate/pet ether gave the pure compound 5a (720 mg, 68% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of compound 4a (700 mg, 5.18 mmol) in THF (10 mL) was added LiHMDS (6.2 ml, 1 M sol. in THF, 6.2 mmol) at 0 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (870 mg, 6.22 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at 0 C and stirred at rt for 4 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 10% ethyl acetate/pet ether gave the pure compound 5a (720 mg, 68% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of compound 4a (700 mg, 5.18 mmol) in THF (10 mL) was added LiHMDS (6.2 ml, 1 M sol. in THF, 6.2 mmol) at 0 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (870 mg, 6.22 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at 0 C and stirred at rt for 4 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 10% ethyl acetate/pet ether gave the pure compound 5a (720 mg, 68% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of phenyl acetic acid ethyl ester 1a (1 g, 6.09 mmol) in THF (10 mL) was added LiHMDS (9.1 ml, 1 M sol. in THF, 7.31 mmol) at -78 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (1.2 g, 9.146 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at -78 C and stirred at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 4% ethyl acetate/pet ether gave the pure compound 3a (1.1 g, 81% yield) as a colorless liquid.
General procedure: To a stirred solution of compound 4a (700 mg, 5.18 mmol) in THF (10 mL) was added LiHMDS (6.2 ml, 1 M sol. in THF, 6.2 mmol) at 0 C and the reaction mixture was stirred at this temperature for 30 min. Ethyl-1-imidazole carboxylate 2 (870 mg, 6.22 mmol) in dry THF (3 ml) was added drop wise to the reaction mixture at 0 C and stirred at rt for 4 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with water, saturated brine solution and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 10% ethyl acetate/pet ether gave the pure compound 5a (720 mg, 68% yield) as a colorless liquid.
With Imidazole hydrochloride; In water; at 20℃; for 0.166667h;
General procedure: In a round bottomed flask 0.01 mol (1.36 g) phenyl acetic acid and 0.012 mol (1.94 g) of CDI were added. The reaction mixture was mixed and grinded with a spatula. CO2 gas starts releasing with increase in temperature and solid reaction mixture was turned to pale yellow liquid within 5 min. 0.001 mol (0.1 g) Imidazole. hydrochloride, 0.01 mol (0.87 g) of morpholine, and 1 mL of water were added to it. The reaction mixture was kept at room temperature for another 10 min. Dilute hydrochloride solution was added to it and the aqueous layer was washed with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and concentrated to give pure product.
With Imidazole hydrochloride; In water; at 20℃; for 0.166667h;
General procedure: In a round bottomed flask 0.01 mol (1.36 g) phenyl acetic acid and 0.012 mol (1.94 g) of CDI were added. The reaction mixture was mixed and grinded with a spatula. CO2 gas starts releasing with increase in temperature and solid reaction mixture was turned to pale yellow liquid within 5 min. 0.001 mol (0.1 g) Imidazole. hydrochloride, 0.01 mol (0.87 g) of morpholine, and 1 mL of water were added to it. The reaction mixture was kept at room temperature for another 10 min. Dilute hydrochloride solution was added to it and the aqueous layer was washed with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and concentrated to give pure product.
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