N-methylsulfamoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methylsulphamoyl chloride (0.39 g) was added dropwise to a stirred solution of 4-[(4-aminophenoxy)methyl]-1-[4-pyridyl]-piperidine (see Preparation 4) (0.57 g) in pyridine (15 ml) and the mixture was stirred at room temperature for 6 hours. An additional 0.39 g of methylsulphamoyl chloride was then added and the mixture was stirred for a further 18 hours and then evaporated. The residue was partitioned between sodium bicarbonate solution and ethyl acetate. The organic layer was separated and the aqueous layer was extracted several times with ethyl acetate. The combined organic layers were washed with water, dried (Na2SO4) and evaporated. The solid residue was crystallised from ethanol to give the title compound, (0.30 g), m.p. 170.5°-172.5°. the mixture was stirred for a further 18 hours evaporated The residue was partitioned between sodium bicarbonate solution and ethyl acetate The organic layer was separated the aqueous layer was extracted several times with ethyl acetate The combined organic layers were washed with water dried (Na2SO4) evaporated The solid residue was crystallised from ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound was prepared according to the procedure used in Example 112. Thus, a mixture of 14.8 g (0.1 mole) of 2-phenoxyethanol (Matheson, Coleman, and Bell), 15.6 g (0.12 mole) of methylsulfamoyl chloride and 12.3 g (0.12 mole) of triethylamine in 150 ml of acetonitrile gave a viscous oil that solidified upon standing. The solid was recrystallized from benzene-petroleum ether (30°-60° C.) to yield 15.4 g (67%) of shiny, white flakes, mp 66°-68° C. This compound was prepared gave a viscous oil that The solid was recrystallized from benzene-petroleum ether (30°-60° C.) to yield 15.4 g (67%) of shiny, white flakes, mp 66°-68° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 12.4 g (0.1 mole) of 2-methoxyphenol (guaiacol; Aldrich) and 13.1 g (0.1 mole) of methylsulfamoyl chloride (Preparation 20) in 150 ml of toluene was stirred and treated at reflux for 2 hr. The solvent was evaporated under reduced pressure and the only residue was purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrePAK 500A silica, ethyl acetate-hexanes, 1:2; flow rate 150 ml/min). Fractions containing the product were combined and the solvents evaporated under reduced pressure to yield an oil that solidified upon standing. The solid was recrystallized from benzene-petroleum-ether (30°-60° C.) to give 14.3 g (66%) of the title compound as a white solid, mp 68°-71° C. treated at reflux for 2 hr The solvent was evaporated under reduced pressure the only residue was purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrePAK 500A silica, ethyl acetate-hexanes, 1:2; flow rate 150 ml/min) Fractions containing the product the solvents evaporated under reduced pressure to yield an oil that The solid was recrystallized from benzene-petroleum-ether (30°-60° C.)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-imidazol-1-yl-phenol (20.0 g, 0.125 mole), 2-chloroethanol (40.25 g, 0.50 mole) and potassium carbonate (69.0 g, 0.50 mol) in 500 ml of methyl ethyl ketone was heated at reflux for 48 hr as its progress was being monitored by TLC (methanol:methylene chloride 10:90). The reaction was then filtered, and the filtrate evaporated to a solid which was redissolved in hot isopropanol. The crystals which formed upon cooling were filtered, rinsed with isopropyl ether, and dried (7.36 g, 28.9% yield, 1H NMR: 95% pure). This intermediate alcohol (6.0 g, 0.029 mole) was suspended in methylene chloride (60 ml) and triethylamine (3.51 g, 0.0348 mole) added to the stirring suspension. The reaction was chilled at 10° C. and methylsulfamoyl chloride (4.51 g, 0.0348 mole) added dropwise allowing reaction to slowly warm to room temperature. After 1 hr of stirring, TLC indicated reaction was not complete so it was treated with additional 0.03 mole of base and methylsulfamoyl chloride and stirred overnight. After the reaction had gone to completion, it was evaporated to a residue. The residue was dissolved in ethyl acetate/acetonitrile (1:1) (200 ml) and washed with sodium bicarbonate/sodium chloride (1:1) (2×200 ml). The organic layer was evaporated and redissolved in hot ethanol. Upon cooling, crystals precipitated and were filtered and dried. They were then dissolved in methanol and anhydrous HCl in isopropyl alcohol added. A carbon filtration was done and the methanol evaporated as more isopropanol was added. Off-white crystals precipitated and were filtered, dried, and analyzed (4.14 g, 42%, mp 85°-88° C.). at reflux for 48 hr as its progress The reaction was then filtered the filtrate evaporated to a solid which was redissolved in hot isopropanol The crystals which formed upon cooling were filtered rinsed with isopropyl ether dried (7.36 g, 28.9% yield, 1H NMR: 95% pure) reaction to slowly warm to room temperature reaction stirred overnight was evaporated to a residue The residue was dissolved in ethyl acetate/acetonitrile (1:1) (200 ml) washed with sodium bicarbonate/sodium chloride (1:1) (2×200 ml) The organic layer was evaporated redissolved in hot ethanol Upon cooling crystals precipitated were filtered dried They were then dissolved in methanol anhydrous HCl in isopropyl alcohol added A carbon filtration the methanol evaporated as more isopropanol was added Off-white crystals precipitated were filtered dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 18.1 g (0.14 mole) of N-methylsulfamoyl chloride (Preparation 24) in 20 ml methylene chloride was added at 10°-20° C. to a solution of 12.8 g (0.10 mole) of 4-chlorophenol and 15 g (0.15 mole) of triethylamine in 50 ml of methylene chloride. The cooling was removed and the mixture stirred at ambient temperature for four hours. The mixture was filtered to remove the triethylamine hydrochloride. The filtrate was extracted with dilute HCl (6 ml of 37% hydrochloric acid in 60 ml water) followed by a water wash. The organic layer was then extracted with dilute potassium carbonate (8.0 g in 80 ml water) followed by a water wash. The methylene chloride layer was concentrated to 21.7 g of yellow oil which crystallized on cooling. The solid was stirred in a mixture of 10 ml toluene and 63 ml petroleum ether to obtain 20.3 g of yellow solid. The 20.3 g was recrystallized from 1:2 toluene: petroleum ether to give 8.73 g of white solid, mp 61°-62° C. The cooling was removed The mixture was filtered to remove the triethylamine hydrochloride The filtrate was extracted with dilute HCl (6 ml of 37% hydrochloric acid in 60 ml water) wash The organic layer was then extracted with dilute potassium carbonate (8.0 g in 80 ml water) wash The methylene chloride layer was concentrated to 21.7 g of yellow oil which crystallized on cooling The solid was stirred in a mixture of 10 ml toluene and 63 ml petroleum ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 26.5 g (0.13 mole) of glycerol guaiacolate in 100 ml of methylene chloride and 10.8 ml (0.13 mole) of pyridine was added in a thin stream to a stirred solution of 17.1 g (0.13 mole) of N-methylsulfamoyl chloride (Preparation 24) in 70 ml of methylene chloride, and the reaction mixture was stirred at ambient temperature for 2 hr. The reaction mixture was treated with 150 ml of water, the layers were separated, and the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water, dried (magnesium sulfate), and the solvent was evaporated under reduced pressure to yield a viscous oil. The oil was purified by preparative high pressure liquid chromatography. Fractions containing the desired product were combined and the solvents evaporated under reduced pressure to give 13.9 g (37%) of the title compound as a yellow gum. the layers were separated the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water dried (magnesium sulfate) the solvent was evaporated under reduced pressure to yield a viscous oil The oil was purified by preparative high pressure liquid chromatography Fractions containing the desired product the solvents evaporated under reduced pressure