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With thionyl chloride |
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With thionyl chloride at 50℃; |
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With thionyl chloride In benzene for 24h; |
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With oxalyl dichloride In chloroform Ambient temperature; |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 0.416667h; |
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With oxalyl dichloride In N,N-dimethyl-formamide; benzene at 0℃; for 2h; |
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With oxalyl dichloride |
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With oxalyl dichloride In dichloromethane for 1h; Ambient temperature; |
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With thionyl chloride; N,N-dimethyl-formamide In chloroform at 35 - 40℃; for 2.5h; |
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With thionyl chloride for 1h; Heating; |
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With thionyl chloride In toluene at 23℃; |
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With thionyl chloride In Carbon tetrachloride at 65℃; for 1.5h; |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h; |
17.A
Example 17 Ethyl (2-ethyl-4-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]quinolin-l-yl)acetate EPO Part A2-Nitrophenylacetic acid (15.0 g, 82.8 mmol) was dissolved in 330 mL of dichloromethane. Three drops of DMF were added, followed by dropwise addition of oxalyl chloride (14.4 mL, 165.6 mmol). The reaction was allowed to stir at ambient temperature for 3 hours, at which time the reaction was concentrated under reduced pressure to afford (2-nitrophenyl)acetyl chloride |
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With thionyl chloride In dichloromethane for 20h; Heating; |
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With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 4h; |
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With thionyl chloride; N,N-dimethyl-formamide In benzene at 20℃; for 20h; |
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With chlorophosphonic acid In toluene at 20℃; |
2 Example 2; N-[(3-Chloro-5-trifluoromethyl-2-pyridyl)methyl]-2-nitrophenylacetamide (Compound 108)
To a stirred suspension of 2-nitrophenylacetic acid (0.36 g) in dry toluene (5 ml) at room temperature was added phosphoryl chloride (0.37 g) and stirring was continued overnight. Meanwhile a solution of the amine was prepared, (3-Chloro-5-trifluoromethyl-2-pyridyl)methylamine hydrochloride (0.49 g) in dry toluene (5 ml) and triethylamine (1.23 g) was stirred at room temperature for 1 hour and then filtered. The solid was washed with dry toluene and the combined filtrates were added dropwise to the above suspension of acid chloride with ice-cooling. After addition, the mixture was stirred at room temperature overnight. Dichloromethane was added and the mixture was washed with water. The aqueous layer was separated and back-extracted with dichloromethane. The combined organic extracts were washed with saturated sodium bicarbonate solution, then brine, then dried (MgSO4), and the solvent removed. The resulting residue was purified by silica gel chromatography eluting with ethyl acetate/light petroleum (b.p. 40-60°C) to give the title product, m.p. 123-4°C |
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With thionyl chloride; N,N-dimethyl-formamide In benzene at 20℃; for 20h; Inert atmosphere; |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 20h; |
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With thionyl chloride In N,N-dimethyl-formamide; toluene at 20℃; Inert atmosphere; |
4.2. General procedure for the preparation of a solution of acid chlorides in CH2Cl2
General procedure: To a solution of carboxylic acids (1.7 mmol) in dry DMF (100 μL) and dry toluene (15 mL) under nitrogen atmosphere, freshly distillated thionyl chloride (3.4 mmol) was added and the solution was stirred at room temperature overnight. The solvent and thionyl chloride were removed under vacuum. The acid chloride was dissolved with dichloromethane (15 mL) under nitrogen atmosphere and directly used for the synthesis of the boronic acid. |
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With thionyl chloride In dichloromethane at 25℃; for 4h; Inert atmosphere; |
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With thionyl chloride |
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With thionyl chloride; N,N-dimethyl-formamide In chloroform at 40℃; Inert atmosphere; |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 25℃; for 1h; Inert atmosphere; |
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With thionyl chloride In dichloromethane for 4h; Reflux; |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 3h; |
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With thionyl chloride at 90℃; |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 4h; Inert atmosphere; |
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With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 7h; Cooling with ice; |
2.2.1. Synthesis of 5-(1-hydroxy-2-(2-nitrophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (4)
General procedure: In a round bottom flask, 250 mg (1.3 mmol) of 2-nitrophenyl-aceticacid (1) was dissolved in dry 15 mL of dichloromethane (DCM). To thissolution, 4 mL (excess) of thionyl chloride (SOCl2) and 5 drops ofdimethylformamide (DMF) were added to an ice bath. The resultingmixture was stirred for 2 h at room temperature and then boiled for 5 hat refilux temperature. After completing the reaction, monitored bycontrol of TLC, solvent and excess of thionyl chloride were removedfrom the reaction medium with an evaporator’s aid. The resulting acylchloride 2 was used for the next step without any purification. The acylchloride 2 was dissolved in dry DCM. Meanwhile, in another flask, 200mg (1.6 mmol) of Meldrum’s acid and 5 mL (3.2 mmol) of Hünig’s basewere dissolved in dry DCM on an ice bath and dropwise added to thesolution. The resulting mixture was stirred for 2 h at 0 C, and the icebath was removed. The resulting mixture was stirred at room temperaturefor an additional 1 h. After completing the reaction, 10 mL of 1 MHCl was added to the reaction medium, and the mixture was extractedwith DCM (3 × 30 mL). Combined organic phases were dried withMgSO4. Evaporation of the solvent gave 340 mg of 5-(1-hydroxy-2-(2-nitrophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (4) as thewhite crystals (85%) |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; Inert atmosphere; |
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With thionyl chloride In dichloromethane at 20℃; for 3h; |
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