Methanesulfonyl chloride solutions

In the glove box, add 320 tL (160 tmol, 2.0 eq) of the methanesulfonyl chloride solution into each test tube. 

TheTnain products of the radiolysis of methanesulfonyl chloride solutions in cyclohexane are methane, and chloro-cyclohexane. In addition, small amounts of methylchloride are also formed. The yields of these products satisfy the material balance relations XI and XII. 

B. cis-1,2-Gyclohexanedimethanol Dimethanesulfonate. In a 5-1., three-necked, round-bottomed flask, immersed in an ice-salt bath and fitted with a mechanical stirrer and an addition funnel, is plaeed a solution of 111 g. (0.97 mole) of methanesulfonyl chloride in 1.21. of pyridine. While cooling and stirring, a solution of 46.4 g. (0.322 mole) of m-l,2-cyclohexanedimethanol in 250 ml. of pyridine is added dropwise at a rate such that the temperature does not exceed 0° (Note 5). Upon completion of the addition, the mixture is stirred at — 5° to 0° for an additional 2 hours. Two liters of cold 10% hydrochloric acid is introduced at a rate which maintains the reaction mixture below 20° (Note 5). The solid which separates is isolated by suction filtration, washed sequentially with 11. of dilute hydrochloric acid and 21. of water, and air-dried. There is isolated 93-95 g. (96-98%) of the dimethanesulfonate having m.p. 66-67.5°. Reorystallization from methanol gives needles melting at 75-76° (Note 6). 

The azido alcohol is dissolved in a minimal amount of dry pyridine and cooled in an ice bath. Methanesulfonyl chloride (1 ml/g of azido alcohol) is added to the cold solution. The reaction mixture is allowed to stand at 0° for 24 to 72 hr. The reaction mixture is processed by pouring into ice water and either filtering the product, if possible, or by extraction with an organic solvent. Methanol or methanol-ether have been used to recrystallize the crude azido mesylates. 

To the epoxide dissolved in a minimal amount of chloroform or ether is added a corresponding solution of freshly prepared thiocyanic acid (20 fold excess) as described above (acetic acid has also been used as solvent). The resulting solution is allowed to stand at least 70 hr at room temperature. (Some workers have protected the reaction mixture from light during this period). The reaction mixture is worked up by washing first with a 10% solution of sodium carbonate, sodium bicarbonate or potassium bicarbonate, and then water. The remaining ether extract is dried (Na2S04) and evaporated under vacuum. The crude thiocyanatohydrin is crystallized from an appropriate solvent or treated with methanesulfonyl chloride s (see below). 

To a stirred solution of 186 mg (0.568 mmol) of methyl 2-hydroxy-2- 2-oxo-5-[(Z)-6-trimcthylsilyl-4-hex-cnyl]pyrrolidinyl acetate in 4.5 mL of acetonitrile, under a nitrogen atmosphere at -30 C, is added 0.095 mL (0.68 mmol) of triethylamine. After 15 min, 0.050 mL (0.64 mmol) of methanesulfonyl chloride is added, and the reaction mixture is allowed to warm to 20 "C and then refluxed for 20 h. After cooling... 

The addition rate is about 30 drops/minute. After about half of the methanesulfonyl chloride has been added, white crystals of pyridine hydrochloride begin to precipitate, and the solution becomes viscous (Note 16). 

The reagent methanesulfonyl chloride-IV,IV-dimethylformamide has been used to prepare 6-chloro-6-deoxyamylose of d.s. 0.8 from the polysaccharide,391 but it was necessary first to convert the amy-lose into a reactive form by freeze-drying its aqueous solution. 

D. N-Benzyl-3-(Z/E)-ethylideneazetidin-2-one. Into a dry, 250-mL, one-necked, round-bottomed flask, fitted with a magnetic stirring bar, is placed 9.60 g (0.047 mol) of N-benzyl-3-(1-hydroxyethyl)azetidin-2-one, 125 mL of dry dichloromethane (Note 10), and 13.0 mL (0.093 mol) of triethylamine. The solution is cooled in an ice bath before 4.0 mL (0.052 mol) of methanesulfonyl chloride (Note 11) is introduced. The mixture is stirred at 0°C for 1 hr, transferred to a separatory funnel, and washed with saturated sodium bicarbonate solution (2 x 150 mL) and brine (200 mL). The organic phase is dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure to leave 14.3 of orange oil (Note 12). 

The solution turns to a white suspension after half of the methanesulfonyl chloride is added methanesulfonyl chloride, available from Tokyo Kasei Kogyo Company, Ltd. (Japan), was used without any purification. 

To a solution of (S,5)-l,3-diphenylpropane-l,3-diol (1.12g, 4.95mmol) and triethylamine (1.63 g, 14.85 mmol) in 25mLTHF at 0 °C was added methanesulfonyl chloride (1.13 g, 9.90 mmol). The mixture was kept at 0 °C for 8 h and then the solvent was removed under reduced pressure at the same temperature. The product was extracted with diethyl ether, washed with water and dried over Na2S04 (1.90 g, quantitative yield). (NMR data.)... 

D. 3,6,9-Tris(p-tolylsulfonyl)-3,6,9-triazaundecane-l,ll-dimeth-anesulfonate (4). A 3-1., three-necked, round-bottomed flask is equipped with a mechanical stirrer, addition funnel, nitrogen inlet, and low-temperature thermometer. The flask is charged with a dried solution of 200 g. (0.306 mole) of diol 3 and 100 ml. of triethylamine in 1500 ml. of methylene chloride (Note 5). The stirred solution is held at -15 to -20° in a dry-ice-acetone bath as 50 ml. (74 g.) of methanesulfonyl chloride (Note 1) is added over 10 minutes. The dry-ice bath is replaced by an ice bath, and the solution is stirred for 30 minutes, poured into a mixture of 11. of crushed ice and 500 ml. of 10% aqueous HC1 solution, and shaken. The layers are separated, and the organic layer is washed with two 500-ml. portions of water and 500 ml. of saturated salt solution, then dried over anhydrous magnesium sulfate. The solution is filtered and evaporated to dryness under reduced pressure to give a white solid, which is dissolved in 250 ml. of methylene chloride and crystallized by addition of 500 ml. of ethyl acetate and cooling in an ice bath. The yield of methanesulfonate 4 is 215-235 g. (87-95%), m.p. 146-148°. 

A solution of 72.08 g (0.19 mol) of 5-bromo-l-pentanyl acetate in 1.4 L of MeOH was treated with 38 mL of a 1.0 molar solution of tetrabutylammonium hydroxide and the mixture was stirred at room temperature for 3.0 h, 3.0 mL of AcOH was added and the solution was evaporated at 35°C. The residue was dissolved in 400 mL of EtOAc and the solution was washed with saturated NaHC03, brine, dried, and evaporated to give 60.45 g (94% yield) of the intermediate hydroxy ester (an analytical sample may be obtained by crystallization from 70% EtOAc in hexane, m.p. 58-61°C. A stirred solution of 60.25 g of the hydroxyester in 700 mL of EtOAc was cooled to 5°C and treated with 75.5 mL (3 equiv.) of triethylamine and 32.6 mL (2.35 equiv.) of methanesulfonyl chloride. The mixture was stirred at 6°C for 2.0 h, transferred to a separatory funnel and washed sequentially with water, 2 N HCI, and brine. Concentration of the EtOAc to ca. 300 mL and dilution cooled to 0°C and treated with 75.5 mL (3 equiv.) of triethylamine and 32.6 mL (2.35 equiv.) of methanesulfonyl chloride. The mixture was stirred at 6°C for 2.0 h transferred to a separatory funnel and washed sequentially with water, 2 N HCI, and brine. Concentration of the EtOAc to ca. 300 mL and dilution with 250 mL of hexane led to crystallization (0°C, 18 h). The product was collected by filtration and washed with some cold hexane - EtOAc (1 1) to give 66 g (84% yield) of methyl (R,S)-6-acetyl-3,4-dihydro-7-[5-[(methylsufonyl)oxy]pentyloxy]-2H-l-benzopyran-2-carboxylate m.p. 73-76°C. 

A mechanically stirred solution of aniline (139.7 g, 1.5 mol) in pyridine (2 L), under N2 is cooled in an icebath. Methanesulfonyl chloride (171.8 g, 1.5 mol) is added dropwise to this solution while the temperature is maintained at 15°-20°C, which results in a red-orange color change in the reaction mixture. 

S)-l-[2-Hydroxy-4-(4-chlorophenyl)butyl]-lH-imidazole nitrate was prepared as follows. To a solution of (2S)-l-(p-toluenesulphonyloxy)-4-(4-chlorophenyl)butan-2-ol (250 mg, 1 mmol) in THF (5 ml) at 0°C was added triethylamine (0.28 ml, 2.0 mmol), followed by methanesulfonyl chloride (0,15 ml, 2.0 mmol). The reaction mixture was was warmed to room temperature and stirred for 1 h. The mixture was poured into aq. NaHC03, extracted with EtOAC, and the organic phase dried and evaporated to dryness. The resulting mesylate was dissolved in acetone (50 ml), then 2,6-dichlorobenzenethiol... 

To a stirred solution of 9a-fluoro-lip,17,21-trihydroxy-16a-methyl-pregna-l,4-diene-3,20-dione (lOg, 25.5 mmol) in 20 ml pyridine and 12 ml acetone at -10°C, a cold solution of methanesulfonyl chloride (3 ml, 38.5 mmol) in 8 ml acetone was added dropwise. The addition was completed within about 3 hours and the mixture was then left standing in the cold for a further IV2 hours after which 200 ml cold water were added. The resulting precipitate was separated by filtration and washed with water to give 11.5 g (96% of theoretical yield) of dexamethasone 21-mesylate, melting point 208°C to 210°C (decomposition). 

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