Dimethylformamide, reaction with methyl sulfate

Cydopentadienylsodium, reaction with dimethylformamide-dimethyl sulfate complex, 47, S3 1,3-Cyclopentanedione, 2-methyl-, 47, 83... 

Reaction of Methyl 4,6-Dichloro-4,6-dideoxy-a-D-galactopyranoside 2,3-Di(chloro-sulfate) with Sodium Azide, and with Sodium Bromide, in A/,2V-Dimethylformamide, H. Parolis, W. A. Szarek, and J. K. N. Jones, Carbohydr. Res., 19 (1975) 97-105. 

To a cold solution of N-Boc-L-serine (32.4 g, 0.16 mol. Note 5) in dimethylformamide (150 ml) is added solid potassium carbonate (24.3 g, 0.176 mol). After stirring for 10 min in an ice-water bath, methyl iodide (20.0 mL, 46.3 g, 0.32 mol -Caution Methyl iodide is toxic and a suspected carcinogen that should be handled in a well-ventilated fume hood.) is added to the white suspension and stirring continued at 0°C for 30 min whereupon the mixture solidifies. The reaction is warmed to room temperature and stirred for an additional hour or so at which point TLC analysis indicates complete formation of the methyl ester (Note 6). The reaction mixture is filtered by suction and the filtrate partitioned between ethyl acetate (300 mL) and water (300 mL). The organic phase is washed with brine (2 x 300 mL), dried with magnesium sulfate, filtered and concentrated to give 29.8 g (86% yield) of N-Boc-L-serine methyl ester as a pale amber oil which is used without further purification (Notes 7 and 8).2... 

Prepares solution of sodium methylate by dissolving 3.9 g of sodium metal in 500 ml of methanol. Add 39.0 g of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazeplne-2-one. Evaporate the reaction mixture to a residue and dissolve the residue in 170 ml of dimethylformamide. Add 30 g of 2,2,2-trifluoroethyl Iodide and stir at room temperature for Vi hour, then heat to 60°C to 70°C for an additional 7 hours. Add 19 g of 2,2,2-trifluoroethyl iodide and resume the heating and stirring at 60°C to 70°C for an additional 16 hours. Filter off the solids and evaporate the filtrate to a residue in vacuo. Triturate the residue with water and extract with ethyl ether. Wash the ethereal extract with water, dry over anhydrous sodium sulfate and evaporate the solvent to a residue. 

The value of methylation studies in structural determination of carbohydrates is well known. Methylation of sucrose has generally been achieved by the use of dimethyl sulfate-sodium hydroxide,34,35 methyl iodide-silver oxide-acetone,20 sodium hydride-methyl io-dide-N,N-dimethylformamide,35 or diazomethane-boron trifluoride etherate.36,37 The last method (already applied to monosaccharides38,39) has been found particularly useful for sucrose, because it proceeds without concomitant migration of acyl groups. The reaction of 2,3,6,T,3, 4, 6 -hepta-0-acetylsucrose (21) and 2,3,4,6,1, 3, 4 -hepta-O-acetylsucrose (22) with diazomethane in dichloromethane in the presence of a catalytic proportion of boron trifluoride etherate for 0.5 h at —5° gave the corresponding 4-methyl (23) and 6 -methyl (24)... 

A solution of 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-l,4-benzoxazine-8-carboxylic acid in tetrahydrofuran and dimethylformamide is cooled to below 0°C and triethylamine is added under stirring thereto. Further, ethyl chlorocarbonate is added and the mixture is stirred at room temperature. To the resultant mixture is added 3-amino-8-azabicyclo[3.2.1]octane and the mixture stirred. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off to give 6-chloro-3,4-dihydro-4-methyl-N-(8-azabicyclo[3.2.1]oct-3-yl)-3-oxo-2H-l,4-benzoxazine-8-carboxamide. 

Methyl-l-piperazinyl)benzimididazole (5.00 g) prepared as above is dissolved in N,N-dimethylformamide (50 ml) and thereto is added sodium hydride (concentration 50%) (1.50 g) at room temperature, and the mixture is stirred for 30 minutes. To the mixture is added 2-bromoethyl ethyl ether (4.00 g), and the mixture is stirred at 70°C for 10 hours. To the reaction mixture is added water (150 ml), and the mixture is extracted with ethyl acetate. The extract is washed with water, dried over anhydrous magnesium sulfate and then concentrated to give a brown oily substance (5.40 g). The brown oily substance is treated with fumaric acid (3.26 g) in hot ethanol. The crude crystals thus obtained are recrystallized from ethyl acetate-ethanol to give l-[2-(ethoxy)ethyl]-2-(4-methyl-l-piperazinyl)benzimidazole 3/2 fumarate (6.31 g) as colorless plates, melting point 167.5°-168.5°C. Elementary analysis for C22H30N4O7 Calcd. (%) C, 57.13 H, 6.54 N, 12.11 Found (%) C, 57.04 H, 6.44 N, 12.02. 

The flask containing the solution of the (+)-(3aS,7aS)-2,3,3a,4,7,7a-hexahydro-3a-hydroxy-7a-methyl-lH-indene-1,5(6H)-dione in N,N-dimethyl -formamide is placed 1n an oil bath and heated to 95°C. When the temperature reaches 70-75°C, an 18.8-mL aliquot of the coned sulfuric acid in N,N-dimethylformamide solution is added in one portion. The reaction mixture is heated to 95°C for 3.0 hr. After 1.0 hr, an additional 7.5-mL aliquot of the coned sulfuric acid in N,N-dimethy1formamide solution is added in one portion. The reaction is monitored for completeness by GLC (Note 15) and cooled. The solvent is removed on a rotary evaporator at 45°C (0.3-0.5 ran) to give a brown oil. The material is taken up in 375 mL of dlchloromethane. The solution is washed with two 190-mL portions of 2.0 N sulfuric acid solution which have been saturated with sodium chloride, two 190-mL portions of saturated sodium bicarbonate solution which have been saturated with sodium chloride and 190 mL of saturated brine. Each aqueous wash is extracted, in turn, with the same two 190-mL portions of dichloromethane. The combined dichloromethane solutions are dried over sodium sulfate, filtered, and the solvent is removed on a rotary evaporator at 40°C (70 mm) to give 38.8-39.6 g of oily, brown semisolid. This material is taken up in 78 mL of ethyl acetate and the solution is applied to a dry column of 78 g of silica gel (Note 16). The column is eluted with 600 mL of ethyl acetate and the total eluate is... 

Chloro-5-(1 -Cyclohexenyl)-1-Methyl-2-Oxo-2,3-Dihydro 1 H-Benzo(f)Diazepine-1,4 9.7 grams of sodium methylate are added to a solution of 16.5 grams of 7-chloro-5-(1 -cyclo-hexenyl)-2-oxo-2,3-dihydro 1 H-benzo(f)diazepine-1,4 dissolved in 120 ml of dry dimethyl-formamide and the mixture stirred for one-half hour. The reaction mixture Is cooled in a water bath and a solution of 33.8 grams of methyl iodide dissolved in 35 ml of anhydrous dimethylformamide is then slowly added with stirring. The solution becomes dark brown in color and a precipitate forms. It is stirred for 2 hours, then diluted with a large volume of water and extracted with ethyl acetate. The ethyl acetate solution is washed with water, dried over anhydrous sodium sulfate and the solvent evaporated under reduced pressure. The residue is crystallized from a small volume of ethyl acetate. Brownish yellow crystals are obtained (9 grams yield, 52%), MP < = 144°C. 

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