Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate
- Iupac Name：ethyl 5-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-4-carboxylate
- CAS No.: 144689-93-0
- Molecular Weight：240.3
- Modify Date.: 2022-11-22 16:56
- Introduction: Olmesartan (O550000) intermediate. Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylateSupplier
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1. Names and Identifiers
- 1.1 Name
- Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate
- 1.2 Synonyms
1H-Imidazole-4-carboxylic acid,5-(1-hydroxy-1-methylethyl)-2- propyl-,ethyl ester 1H-Imidazole-4-carboxylicacid,5-(1-hydroxy-1-met 1H-Imidazole-5-carboxylic acid, 4-(1-hydroxy-1-methylethyl)-2-propyl-, ethyl ester 1H-Imidazole-5-carboxylicacid,4-(1-hydroxy-1-met 4-(1-Hydroxy-1-methylethyl)-2-propyl 4-(1-Hydroxy-1-methylethyl)-2-propyl- 4-(1-HYDROXY-1-METHYLETHYL)-2-PROPYL-1H-IMIDAZOLE-5-CARBOXYLIC ACID ETHYL ESTER 4-(2-Hydroxy-2-propyl)-2-propyl-1H-imidazole-5-carboxylic Acid Ethyl Ester 5-(1-HYDROXYL-1-METHYLETHYL)-2-PROPYL-IMIDAZOL-4-YLCARBOXYLIC ACID ETHYL ESTER Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate Ethyl 4-(2-hydroxy-2-propanyl)-2-propyl-1H-imidazole-5-carboxylate Ethyl 4-(2-Hydroxy-2-propyl)-2-propyl-1H-imidazole-5-carboxylate ETHYL-4-(1-HYDROXY-1-METHYLETHYL)-2-PROPYL-IMIDAZOLE-5-CARBOXYLATE MFCD07787565 Olmesartan intermediate T5M CNJ B3 DXQ1&1 EVO2
- 1.3 CAS No.
- 144689-93-0
- 1.4 CID
- 10562026
- 1.5 EINECS(EC#)
- 604-434-7
- 1.6 Molecular Formula
- C12H20N2O3 (isomer)
- 1.7 Inchi
- InChI=1S/C12H20N2O3/c1-5-7-8-13-9(11(15)17-6-2)10(14-8)12(3,4)16/h16H,5-7H2,1-4H3,(H,13,14)
- 1.8 InChkey
- KZBJJAFGNMRRHN-UHFFFAOYSA-N
- 1.9 Canonical Smiles
- CCCC1=NC(=C(N1)C(C)(C)O)C(=O)OCC
- 1.10 Isomers Smiles
- CCCC1=NC(=C(N1)C(C)(C)O)C(=O)OCC
2. Properties
- 2.1 Density
- 1.131
- 2.1 Melting point
- 98-100°C
- 2.1 Boiling point
- 456.2°Cat760mmHg
- 2.1 Refractive index
- 1.521
- 2.1 Flash Point
- 229.7°C
- 2.1 Precise Quality
- 240.14700
- 2.1 PSA
- 75.21000
- 2.1 logP
- 1.76630
- 2.1 Storage
- Refrigerator
- 2.2 Chemical Properties
- Pale Yellow Solid
- 2.3 pKa
- 11.61±0.10(Predicted)
- 2.4 StorageTemp
- Sealed in dry,2-8°C
3. Use and Manufacturing
- 3.1 Methods of Manufacturing
- Preparation of Ethyl-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate To a 3M solution of MeMgCl(55.86 g, 0.74 mol) in tetrahydrofuran was added a solution of diethyl 2-propyl imidazole- 4, 5-dicarboxylate (50 g, 0.19 mol) in tetrahydrofuran (200 ml) at -10 to 0°C under NMethyl bromide gas (35 g, 0.3686 mol) was passed through a dry solution of tetrahydrofuran (100 mL) and a small portion (5 to 10 mL) of this solution was added dropwise to a solution of magnesium strip (8 g, 0.33 mol) The solution of iodine (0.02g) and dry tetrahydrofuran (50mL) was stirred at room temperature. After the reaction was initiated, the solution of the remaining methyl bromide in THF was slowly added dropwise to keep the reaction slightly boiling. After the addition was complete, the reaction was continued for 3h until the magnesium strip disappeared. Get the corresponding Grignard reagent;The imidazole diesters of the compounds of the formula II 15g (0.059mol) was dissolved in dry dichloromethane (50mL), slowly added dropwise to the homemade format reagents, the dropping period, maintaining the temperature of the reaction system below 15 °C, after the addition was complete, the control The reaction was continued stirring at a temperature of 15 ~ 25 °C for 2h, after the reaction was cooled to 0 °C, further diluted with ethyl acetate (150mL), and then saturated amine chloride solution (100mL) was slowly added dropwise The process of maintaining the system temperature below 10 °C, dropping completed, the organic layer was collected by stratification, washed with saturated sodium chloride solution (30mLX3), and then dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to remove the solvent To give a residue. The resulting residue was recrystallized from isopropyl ether-n-hexane solvent, filtered and dried to give a white powdery solid 4- (1-hydroxy-1-methylethyl) -2-propyl- 1H-imidazole-5-carboxylate (13.8 g, yield: 97.5percent , HPLC: 99.7percent)100 g (4.16 mol) of magnesium powder was added to tetrahydrofuran (2 L)At 60 ° C into the methyl chloride gas to magnesium powder all disappeared (about 3 hours), And then reflux for 30 minutes, Cold to room temperature, A solution of gray magnesium chloride in methylmagnesium chloride in tetrahydrofuran was prepared.A solution of ethyl 2-propylimidazole-4, 5-dicarboxylate (2) (211.9 g, 0.83 mol) in 2.1 L tetrahydrofuran was added dropwise at 30 ° C.2 hours plus finished, Stirring was continued for 30 minutes.The solvent was removed under reduced pressure and the residue was added dropwise to a solid solution of saturated ammonium chloride solution. Add ethyl acetate 2.5L, the organic layer, the water layer and then ethyl acetate 500ml X 2 extraction, organic layer merger. Wash with saturated salt once. Dried over anhydrous magnesium sulfate. The solvent was evaporated to give pale yellow oil 1 (160.2 g, 80percent) with an APLC purity of 92.91percent, with ketone ethyl ester impurity 3 being 5.04percent.0 grams of 4, 4-dimethyl-2-propyl-4, 6-dihydrofuro [3, 4-d] imidazole (formula II) from Example 1, 30 ml of ethanol and 0.1 ml of concentrated sulfuric acid were added into 100 ml three-necked flask and stirred until completely dissolved, heated to 40-50°C and maintained at that temperature until the reaction completed. The reaction mixture was then allowed to cool to ambient temperature, the solvent was evaporated, 30 ml of ethyl acetate and 30 ml of water were added, and the mixture was adjusted to basic using sodium bicarbonate, The organic layer was separated and the aqueous layer was further extracted with 10 ml x 3 of ethyl acetate. The organic portion was washed once with saturated saline solution, dried over anhydrous magnesium sulfate and filtered, the solvent was evaporated to give 3.4 grams of ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate, resulting in a yield of 92percent..3.0 grams of 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid (formula III) from Example 4, 30 ml of ethanol, and 3.36 grams of thionyl chloride were added into 100 ml three-necked flask, and refluxed until the reaction completed. The reaction mixture was then allowed to cool to ambient temperature, the solvent was evaporated, 30 ml of ethyl acetate and 30 ml of water were added, and the mixture was adjusted to basic using sodium bicarbonate. The organic layer was separated and the aqueous layer was further extracted with 10 ml x 3 of ethyl acetate. The organic portion was washed once with saturated saline solution, dried over anhydrous magnesium sulfate and filtered, the solvent was evaporated to give 2.9 grams of ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate, resulting in a yield of 85percent.
- 3.2 Usage
- Olmesartan (O550000) intermediate. Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylateSupplier
4. Safety and Handling
- 4.1 Hazard Declaration
- H315
- 4.1 Caution Statement
- P261, P264, P271, P272, P273, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P333+P313, P337+P313, P362, P363, P391, P403+P233, P405, P501
- 4.1 Specification
-
The [5-(1-Hydroxyl-1-methylethyl)-2-propyl-imidazol-4-yl]carboxylic acid ethyl ester, with its?CAS registry number 144689-93-0, has the systematic name of ethyl 5-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-4-carboxylate. As to its usage, it is usually applied in the intermediate of antihypertensive agent of Olmesartan, with its product categories including Intermediatesof; Imidazol&Benzimidazole; API intermediates.?
The physical properties of this chemical are as below: (1)ACD/LogP: 1.95; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): 1; (4)ACD/LogD (pH 7.4): 1; (5)ACD/BCF (pH 5.5): 2; (6)ACD/BCF (pH 7.4): 2; (7)ACD/KOC (pH 5.5): 54; (8)ACD/KOC (pH 7.4): 58; (9)#H bond acceptors: 5; (10)#H bond donors: 2; (11)#Freely Rotating Bonds: 7; (12)Polar Surface Area: 75.21 ; (13)Index of Refraction: 1.521; (14)Molar Refractivity: 64.655 cm3; (15)Molar Volume: 212.39 cm3; (16)Polarizability: 25.631×10-24 cm3; (17)Surface Tension: 44.004 dyne/cm; (18)Density: 1.131 g/cm3; (19)Flash Point: 229.723 °C; (20)Enthalpy of Vaporization: 75.462 kJ/mol; (21)Boiling Point: 456.234 °C at 760 mmHg.?
In addition, you could convert the following datas into the molecular structure:
(1)SMILES:O=C(OCC)c1nc(nc1C(O)(C)C)CCC
(2)InChI:InChI=1/C12H20N2O3/c1-5-7-8-13-9(11(15)17-6-2)10(14-8)12(3,4)16/h16H,5-7H2,1-4H3,(H,13,14)?
(3)InChIKey:KZBJJAFGNMRRHN-UHFFFAOYAT
5. MSDS
2.Hazard identification
2.1 Classification of the substance or mixture
Not classified.
2.2 GHS label elements, including precautionary statements
| Pictogram(s) | No symbol. |
| Signal word | No signal word. |
| Hazard statement(s) | none |
| Precautionary statement(s) | |
| Prevention | none |
| Response | none |
| Storage | none |
| Disposal | none |
2.3 Other hazards which do not result in classification
none
7. Synthesis Route
144689-93-0Total: 9 Synthesis Route
9. Other Information
- 9.0 Uses
- An Olmesartan (O550000) intermediate.
- 9.1 Chemical Properties
- Pale Yellow Solid
- 9.2 Uses
- Olmesartan (O550000) intermediate.
- 9.3 Storage Conditions
- Preparation of Ethyl-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate To a 3M solution of MeMgCl(55.86 g, 0.74 mol) in tetrahydrofuran was added a solution of diethyl 2-propyl imidazole- 4, 5-dicarboxylate (50 g, 0.19 mol) in tetrahydrofuran (200 ml) at -10 to 0°C under NMethyl bromide gas (35 g, 0.3686 mol) was passed through a dry solution of tetrahydrofuran (100 mL) and a small portion (5 to 10 mL) of this solution was added dropwise to a solution of magnesium strip (8 g, 0.33 mol) The solution of iodine (0.02g) and dry tetrahydrofuran (50mL) was stirred at room temperature. After the reaction was initiated, the solution of the remaining methyl bromide in THF was slowly added dropwise to keep the reaction slightly boiling. After the addition was complete, the reaction was continued for 3h until the magnesium strip disappeared. Get the corresponding Grignard reagent;The imidazole diesters of the compounds of the formula II 15g (0.059mol) was dissolved in dry dichloromethane (50mL), slowly added dropwise to the homemade format reagents, the dropping period, maintaining the temperature of the reaction system below 15 °C, after the addition was complete, the control The reaction was continued stirring at a temperature of 15 ~ 25 °C for 2h, after the reaction was cooled to 0 °C, further diluted with ethyl acetate (150mL), and then saturated amine chloride solution (100mL) was slowly added dropwise The process of maintaining the system temperature below 10 °C, dropping completed, the organic layer was collected by stratification, washed with saturated sodium chloride solution (30mLX3), and then dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to remove the solvent To give a residue. The resulting residue was recrystallized from isopropyl ether-n-hexane solvent, filtered and dried to give a white powdery solid 4- (1-hydroxy-1-methylethyl) -2-propyl- 1H-imidazole-5-carboxylate (13.8 g, yield: 97.5percent , HPLC: 99.7percent)100 g (4.16 mol) of magnesium powder was added to tetrahydrofuran (2 L)At 60 ° C into the methyl chloride gas to magnesium powder all disappeared (about 3 hours), And then reflux for 30 minutes, Cold to room temperature, A solution of gray magnesium chloride in methylmagnesium chloride in tetrahydrofuran was prepared.A solution of ethyl 2-propylimidazole-4, 5-dicarboxylate (2) (211.9 g, 0.83 mol) in 2.1 L tetrahydrofuran was added dropwise at 30 ° C.2 hours plus finished, Stirring was continued for 30 minutes.The solvent was removed under reduced pressure and the residue was added dropwise to a solid solution of saturated ammonium chloride solution. Add ethyl acetate 2.5L, the organic layer, the water layer and then ethyl acetate 500ml X 2 extraction, organic layer merger. Wash with saturated salt once. Dried over anhydrous magnesium sulfate. The solvent was evaporated to give pale yellow oil 1 (160.2 g, 80percent) with an APLC purity of 92.91percent, with ketone ethyl ester impurity 3 being 5.04percent.0 grams of 4, 4-dimethyl-2-propyl-4, 6-dihydrofuro [3, 4-d] imidazole (formula II) from Example 1, 30 ml of ethanol and 0.1 ml of concentrated sulfuric acid were added into 100 ml three-necked flask and stirred until completely dissolved, heated to 40-50°C and maintained at that temperature until the reaction completed. The reaction mixture was then allowed to cool to ambient temperature, the solvent was evaporated, 30 ml of ethyl acetate and 30 ml of water were added, and the mixture was adjusted to basic using sodium bicarbonate, The organic layer was separated and the aqueous layer was further extracted with 10 ml x 3 of ethyl acetate. The organic portion was washed once with saturated saline solution, dried over anhydrous magnesium sulfate and filtered, the solvent was evaporated to give 3.4 grams of ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate, resulting in a yield of 92percent..3.0 grams of 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid (formula III) from Example 4, 30 ml of ethanol, and 3.36 grams of thionyl chloride were added into 100 ml three-necked flask, and refluxed until the reaction completed. The reaction mixture was then allowed to cool to ambient temperature, the solvent was evaporated, 30 ml of ethyl acetate and 30 ml of water were added, and the mixture was adjusted to basic using sodium bicarbonate. The organic layer was separated and the aqueous layer was further extracted with 10 ml x 3 of ethyl acetate. The organic portion was washed once with saturated saline solution, dried over anhydrous magnesium sulfate and filtered, the solvent was evaporated to give 2.9 grams of ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate, resulting in a yield of 85percent.
10. Computational chemical data
- Molecular Weight: 240.3g/mol
- Molecular Formula: C12H20N2O3
- Compound Is Canonicalized: True
- XLogP3-AA: 1.5
- Exact Mass: 240.14739250
- Monoisotopic Mass: 240.14739250
- Complexity: 269
- Rotatable Bond Count: 6
- Hydrogen Bond Donor Count: 2
- Hydrogen Bond Acceptor Count: 4
- Topological Polar Surface Area: 75.2
- Heavy Atom Count: 17
- Defined Atom Stereocenter Count: 0
- Undefined Atom Stereocenter Count: 0
- Defined Bond Stereocenter Count: 0
- Undefined Bond Stereocenter Count: 0
- Isotope Atom Count: 0
- Covalently-Bonded Unit Count: 1
- CACTVS Substructure Key Fingerprint: AAADceBzMAAAAAAAAAAAAAAAAAAAAWAAAAAAAAAAAAAAAAABgAAAHgAQCAAADEyhlwIDmBbJlgCoAQbwbAQAgC2nEKABGQGwWEiCbhpAqCgXUYAuEALYeWLKAAAMAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==
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12. Realated Product Infomation
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