Structure of 14966-09-7
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CAS No. : | 14966-09-7 |
Formula : | C8H7ClO |
M.W : | 154.59 |
SMILES Code : | O=CC1=CC(C)=CC=C1Cl |
MDL No. : | MFCD12025212 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-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 titanium tetrachloride; In dichloromethane; at 20℃; for 15.0h; | To a solution of 4-chlorotoluene (25.0 g) and dichloromethylmethylether (45.4 g) in dichloromethane (160 ml) was added dropwise at room temperature a solution of titanium tetrachloride (74.9 g) in dichloromethane (40 ml), and the mixture was stirred at the same temperature for 15 hours. The reaction solution was poured into ice, and the organic layer was washed with water, sodium hydrogen carbonate solution, water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was subjected to silica gel column chromatography (ethyl acetate-hexane) to give oil of crude 2-chloro-5-methylbenzaldehyde (18.3 g) and 5-chloro-2-methylbenzaldehyde (4.1 g), respectively. To a mixture of acetone (160 ml), sodium hydroxide (2.6 g) and water (160 ml) was added dropwise at 0 C. a solution of crude 2-chloro-5-methylbenzaldehyde (18.3 g) in acetone (30 ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(2-chloro-5-methylphenyl)-3-buten-2-one (18.9 g) as oil. To a solution of 20% sodium ethoxide in ethanol (4.3 g) was added at room temperature diethyl malonate (10.1 g), and then added little by little 4-(2-chloro-5-methylphenyl)-3-buten-2-one (18.9 g). The mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (33 ml), and the mixture was refluxed for 2 hours and cooled. To the mixture was added 2.5M sulfuric acid (33 ml) for 15 minutes, and the mixture was refluxed for 30 minutes and cooled. Precipitated crystals were filtered and washed with water and isopropylether to give 5-(2-chloro-5-methylphenyl)cyclohexane-1,3-dione (7.8 g) as colorless crystals. mp 186-188 C. 1H-NMR(CDCl3) delta: 2.33 (3H, s), 2.38-2.72 (4H, m), 3.2-5.4 (1H, br), 3.73-3.93 (1H, m), 5.55 (1H, s), 7.01 (1H, d, J=8 Hz), 7.03 (1H, s), 7.26 (1H, d, J=8 Hz). To a mixture of acetone (80 ml), sodium hydroxide (1.2 g) and water (80 ml) was added dropwise at 0 C. a solution of 5-chloro-2-methylbenzaldehyde (4.1 g) in acetone (10 ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(5-chloro-2-methylphenyl)-3-buten-2-one (5.5 g) as oil. To a solution of 20% sodium ethoxide in ethanol (9.5 g) was added at room temperature diethyl malonate (4.5 g) and then added little by little 4-(5-chloro-2-methylphenyl)-3-buten-2-one (5.5 g). The mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (15 ml), and the mixture was refluxed for 2 hours and cooled. To the mixture was added 2.5M sulfuric acid (15 ml) for 15 minutes, and the mixture was refluxed for 30 minutes and cooled. Precipitated crystals were filtered and washed with water and isopropylether to give 5-(5-chloro-2-methylphenyl)cyclohexane-1,3-dione (2.9 g) as colorless crystals. mp 180-181 C. 1H-NMR(CDCl3-DMSO-d6) delta: 2.31 (3H, s), 2.35-2.84 (4H, m), 3.37-3.73 (1H, m), 5.56 (1H, s), 6.9-7.43 (1H, br), 7.08-7.26 (3H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; at 0℃; for 1.0h; | To a solution of 4-chlorotoluene (25.0 g) and dichloromethylmethylether (45.4 g) in dichloromethane (160 ml) was added dropwise at room temperature a solution of titanium tetrachloride (74.9 g) in dichloromethane (40 ml), and the mixture was stirred at the same temperature for 15 hours. The reaction solution was poured into ice, and the organic layer was washed with water, sodium hydrogen carbonate solution, water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was subjected to silica gel column chromatography (ethyl acetate-hexane) to give oil of crude <strong>[14966-09-7]2-chloro-5-methylbenzaldehyde</strong> (18.3 g) and 5-chloro-2-methylbenzaldehyde (4.1 g), respectively. To a mixture of acetone (160 ml), sodium hydroxide (2.6 g) and water (160 ml) was added dropwise at 0 C. a solution of crude <strong>[14966-09-7]2-chloro-5-methylbenzaldehyde</strong> (18.3 g) in acetone (30 ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(2-chloro-5-methylphenyl)-3-buten-2-one (18.9 g) as oil. To a solution of 20% sodium ethoxide in ethanol (4.3 g) was added at room temperature diethyl malonate (10.1 g), and then added little by little 4-(2-chloro-5-methylphenyl)-3-buten-2-one (18.9 g). The mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (33 ml), and the mixture was refluxed for 2 hours and cooled. To the mixture was added 2.5M sulfuric acid (33 ml) for 15 minutes, and the mixture was refluxed for 30 minutes and cooled. Precipitated crystals were filtered and washed with water and isopropylether to give 5-(2-chloro-5-methylphenyl)cyclohexane-1,3-dione (7.8 g) as colorless crystals. mp 186-188 C. 1H-NMR(CDCl3) delta: 2.33 (3H, s), 2.38-2.72 (4H, m), 3.2-5.4 (1H, br), 3.73-3.93 (1H, m), 5.55 (1H, s), 7.01 (1H, d, J=8 Hz), 7.03 (1H, s), 7.26 (1H, d, J=8 Hz). To a mixture of acetone (80 ml), sodium hydroxide (1.2 g) and water (80 ml) was added dropwise at 0 C. a solution of 5-chloro-2-methylbenzaldehyde (4.1 g) in acetone (10 ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(5-chloro-2-methylphenyl)-3-buten-2-one (5.5 g) as oil. To a solution of 20% sodium ethoxide in ethanol (9.5 g) was added at room temperature diethyl malonate (4.5 g) and then added little by little 4-(5-chloro-2-methylphenyl)-3-buten-2-one (5.5 g). The mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (15 ml), and the mixture was refluxed for 2 hours and cooled. To the mixture was added 2.5M sulfuric acid (15 ml) for 15 minutes, and the mixture was refluxed for 30 minutes and cooled. Precipitated crystals were filtered and washed with water and isopropylether to give 5-(5-chloro-2-methylphenyl)cyclohexane-1,3-dione (2.9 g) as colorless crystals. mp 180-181 C. 1H-NMR(CDCl3-DMSO-d6) delta: 2.31 (3H, s), 2.35-2.84 (4H, m), 3.37-3.73 (1H, m), 5.56 (1H, s), 6.9-7.43 (1H, br), 7.08-7.26 (3H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium hydroxide; phosphorus pentachloride; phosphorus trichloride; In N-methyl-acetamide; methanol; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dichloromethane; chloroform; | EXAMPLE 17 4-Chloro-3-(trichlorovinyl)toluene A cold (-10 C.) solution of <strong>[14966-09-7]2-chloro-5-methylbenzaldehyde</strong> (20.8 g) and chloroform (16.6 ml) in 81 ml of dimethylformamide (DMF) is treated dropwise with a methanolic KOH solution (6.08 g in 18.3 ml). The reaction mixture is stirred for 2 hours at -10 C. and then poured into a mixture of 1N HCl (185 ml) and 185 ml of CH2 Cl2. The layers are separated and the aqueous layer further extracted with CH2 Cl2 (2*75 ml). The combined organic layers are washed with water (3x), dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The residue (40 g) was chromatographed on silica with 1:1 hexane/CH2 Cl2 to give 24.49 g of trichloromethyl carbinol. To a suspension of PCl5 (12.4 g) in 250 ml of CH2 Cl2, a solution of the trichloromethyl carbinol (24.49 g) in 100 ml of CH2 Cl2 was added dropwise. The reaction mixture was stirred for 15 minutes at which point an additional 7.5 g of PCl3 was added. The reaction mixture was stirred for an additional hour at room temperature and then carefully poured into 500 ml of ice-water. The layers were separated and the organic layer was washed with water, saturated NaHCO3 solution, and water again. Evaporation afforded 25 g of an oil which was chromatographed on silica (petroleum ether) to give 18.6 g of the pentachloride adduct. This pentachloride adduct (17.6 g) was added to a solution of 3.1 g of NaOH in 150 ml of methanol and the resulting mixture stirred for 16.5 hours at room temperature. The reaction mixture was neutralized with HCl (pH 6) and then concentrated under reduced pressure. The residue was partitioned between ether (400 ml) and water (100 ml). The layers were separated and the organic layer further washed with water and then dried with anhydrous magnesium sulfate. Concentration gave an oil which was distilled at 93-95/3 mm to give pure 4-chloro-3-(trichlorovinyl)toluene, 14.0 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide;titanium tetrachloride; In dichloromethane; water; acetone; | Synthesis of (+-)-7-(5-chloro-2-methylphenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline [Compound 6] Reference Example 20 To a solution of 4-chlorotoluene (25.0g) and dichloromethylmethylether (45.4g) in dichloromethane (160ml) was added dropwise at room temperature a solution of titanium tetrachloride (74.9g) in dichloromethane (40ml), and the mixture was stirred at the same temperature for 15 hours. The reaction solution was poured into ice, and the organic layer was washed with water, sodium hydrogen carbonate solution, water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was subjected to silica gel column chromatography (ethyl acetate-hexane) to give oil of crude <strong>[14966-09-7]2-chloro-5-methylbenzaldehyde</strong> (18.3g) and 5-chloro-2-methylbenzaldehyde (4.1g), respectively. To a mixture of acetone (160ml), sodium hydroxide (2.6g) and water (160ml) was added dropwise at 0C a solution of crude <strong>[14966-09-7]2-chloro-5-methylbenzaldehyde</strong> (18.3g) in acetone (30ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(2-chloro-5-methylphenyl)-3-buten-2-one (18.9g) as oil. |