benzyl methanesulfonate

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

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen methylene chloride (1.4 liter), benzyl alcohol (129.6 g., 1.2 moles) and triethylamine (182 g., 1.8 moles) were combined, stirred and cooled to -5° C. in an ice-water-acetone bath. A solution of methanesulfonyl chloride (150 g., 1.31 moles) in 100 ml. of methylene chloride was added over 49 minutes, maintaining the temperature between -5° and 2° C. After stirring for 10 minutes at 0°-2° C., the reaction was diluted with 500 ml. of water, precooled to 5° C. The organic layer was separated, washed 2×500 ml. of cold water, dried over MgSO4, filtered and evaporated in vacuo to yield title product as a light yellow oil [190 g.; 85%; 1H-NMR (CDCl3) delta (ppm): 2.9 (s, 3H), 5.2 (s, 2H), 7.4 (m, 5H); Rf 0.75 (CH2Cl 2)]. This product was refrigerated until used in the next step. maintaining the temperature between -5° and 2° C After stirring for 10 minutes at 0°-2° C. the reaction was diluted with 500 ml precooled to 5° C The organic layer was separated washed 2×500 ml of cold water, dried over MgSO4 filtered evaporated in vacuo

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

Procedure: Mesyl chloride (25.8 mg) and triethylamine (0.055 ml) were added to a chloroform (0.9 ml) solution of benzyl alcohol (16.2 mg), and the mixture was stirred for 3 hours at room temperature. The reaction mixture was eluted by NH-type silica gel (Chromatorex, Fuji Silysia Chemical Ltd.) column chromatography using tetrahydrofuran as a solvent to obtain methanesulfonic acid benzyl ester. To a tetrahydrofuran (0.9 ml) solution of the methanesulfonic acid benzyl ester, 4-chloro-N-[(1R)-1-(4-ethyl-5-mercapto-4H-1,2,4-triazol-3-yl)ethyl]benzenesulfonamide (Compound 90) (17.3 mg) obtained by performing the same procedure as in Example 1 using the corresponding raw materials, and potassium t-butoxide (8.4 mg) were added, followed by stirring the mixture for 20 hours at 40° C. PSA (polymer supported amine) (0.15 ml) was added to the reaction mixture, and the resulting mixture was stirred for 4 hours at room temperature. The reaction mixture was eluted with ethyl acetate and tetrahydrofuran, and the solvents were distilled off. The resulting residue was eluted by NH-type silica gel column chromatography using tetrahydrofuran as a solvent, and the eluate was purified by silica gel column chromatography to obtain Compound 5 (2.3 mg). The reaction mixture was eluted by NH-type silica gel (Chromatorex, Fuji Silysia Chemical Ltd.) column chromatography

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

Procedure: To a solution of 19.5 g (0.1 mol) 4-thiocyano-2-nitroaniline in 130 ml dimethylformamide is added 3.78 g (0.1 mol) sodium borohydride, all at once. The mixture is stirred for one-half hour, then 15.2 g (0.1 mol) benzyl methanesulfonate in 70 ml dimethylformamide is added. The solution is stirred at 30° for 3 hours, cooled and partitioned between water and dichloromethane. The layers are separated and the aqueous phase reextracted with dichloromethane. The organic phases are combined, washed with aqueous K2CO3, water and saturated NaCl, dried, filtered and stripped to yield 4-(benzyl)sulfenyl-2-nitroaniline. The solution is stirred at 30° for 3 hours cooled partitioned between water and dichloromethane The layers are separated washed with aqueous K2CO3, water and saturated NaCl dried filtered

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

Procedure: To an ice cooled solution of 54 g (0.5 mol) of benzyl alcohol and 75.75 g (104.3 ml, 0.75 mol) of triethylamine in 1800 ml of dichloromethane is added dropwise 63 g (42.57 ml, 0.55 mol) of methanesulfonyl chloride. The temperature of the reaction mixture during the addition is ca. 10°. The reaction mixture is then stirred for 1.5 hours at 10°. The reaction mixture is then diluted with dichloromethane, washed with ice water, cold 10% HCl, saturated KHCO3, saturated NaCl and dried (MgSO4). Solvent is removed in vacuo to yield the benzyl methanesulfonate as an oil. The temperature of the reaction mixture during the addition is ca. 10° washed with ice water, cold 10% HCl, saturated KHCO3, saturated NaCl dried (MgSO4) Solvent is removed in vacuo

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

Procedure: To an ice cooled solution of 54 g (0.5 mol) of benzyl alcohol and 75.75 g (104.3 ml, 0.75 mol) of triethylamine in 1800 ml of dichloromethane is added dropwise 63 g (42.57 ml, 0.55 mol) of methanesulfonyl chloride. The temperature of the reaction mixture during the addition is ca. 10°. The reaction mixture is then stirred for 1.5 hours at 10°. The reaction mixture is then diluted with dichloromethane, washed with ice water, cold 10% HCl, saturated KHCO3, saturated NaCl and dried (MgSO4). Solvent is removed in vacuo to yield the benzyl methanesulfonate as an oil. The temperature of the reaction mixture during the addition is ca. 10° washed with ice water, cold 10% HCl, saturated KHCO3, saturated NaCl dried (MgSO4) Solvent is removed in vacuo

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen methylene chloride (1.4 liter), benzyl alcohol (129.6 g., 1.2 moles) and triethylamine (182 g., 1.8 moles) were combined, stirred and cooled to -5° C. in an ice-water-acetone bath. A solution of methanesulfonyl chloride (150 g., 1.31 moles) in 100 ml. of methylene chloride was added over 49 minutes, maintaining the temperature between -5° and 2° C. After stirring for 10 minutes at 0°-2° C., the reaction was diluted with 500 ml. of water, precooled to 5° C. The organic layer was separated, washed 2×500 ml. of cold water, dried over MgSO4, filtered and evaporated in vacuo to yield title product as a light yellow oil [190 g.; 85%, 1H-NMR (CDCl3) delta (ppm): 2.9 (s, 3H), 5.2 (s, 2H), 7.4 (m, 5H); Rf 0.75 (CH2Cl2 )]. This product was refrigerated until used in the next step. maintaining the temperature between -5° and 2° C After stirring for 10 minutes at 0°-2° C. the reaction was diluted with 500 ml precooled to 5° C The organic layer was separated washed 2×500 ml of cold water, dried over MgSO4 filtered evaporated in vacuo

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen methylene chloride (1.4 liter), benzyl alcohol (129.6 g., 1.2 moles) and triethylamine (182 g., 1.8 moles) were combined, stirred and cooled to -5° C. in an ice-water-acetone bath. A solution of methanesulfonyl chloride (150 g., 1.31 moles) in 100 ml. of methylene chloride was added over 49 minutes, maintaining the temperature between -5° and 2° C. After stirring for 10 minutes at 0°-2° C., the reaction was diluted with 500 ml. of water, precooled to 5° C. The organic layer was separated, washed 2×500 ml. of cold water, dried over MgSO4, filtered and evaporated in vacuo to yield title product as a light yellow oil [190 g.; 85%; 1H-NMR (CDCl3) delta (ppm): 2.9 (s, 3H), 5.2 (s, 2H), 7.4 (m, 5H); Rf 0.75 (CH2Cl 2)]. This product was refrigerated until used in the next step. maintaining the temperature between -5° and 2° C After stirring for 10 minutes at 0°-2° C. the reaction was diluted with 500 ml precooled to 5° C The organic layer was separated washed 2×500 ml of cold water, dried over MgSO4 filtered evaporated in vacuo

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

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen methylene chloride (1.4 liter), benzyl alcohol (129.6 g., 1.2 moles) and triethylamine (182 g., 1.8 moles) were combined, stirred and cooled to -5° C. in an ice-water-acetone bath. A solution of methanesulfonyl chloride (150 g., 1.31 moles) in 100 ml. of methylene chloride was added over 49 minutes, maintaining the temperature between -5° and 2° C. After stirring for 10 minutes at 0°-2° C., the reaction was diluted with 500 ml. of water, precooled to 5° C. The organic layer was separated, washed 2×500 ml. of cold water, dried over MgSO4, filtered and evaporated in vacuo to yield title product as a light yellow oil [190 g.; 85%; 1H--NMR (CDCl3) delta (ppm): 2.9 (s, 3H), 5.2 (s, 2H), 7.4 (m, 5H); Rf 0.75 (CH2Cl 2)]. This product was refrigerated until used in the next step. maintaining the temperature between -5° and 2° C After stirring for 10 minutes at 0°-2° C. the reaction was diluted with 500 ml precooled to 5° C The organic layer was separated washed 2×500 ml of cold water, dried over MgSO4 filtered evaporated in vacuo

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen methylene chloride (1.4 liter), benzyl alcohol (129.6 g., 1.2 moles) and triethylamine (182 g., 1.8 moles) were combined, stirred and cooled to -5° C. in an ice-water-acetone bath. A solution of methanesulfonyl chloride (150 g., 1.31 moles) in 100 ml. of methylene chloride was added over 49 minutes, maintaining the temperature between -5° and 2° C. After stirring for 10 minutes at 0°-2° C., the reaction was diluted with 500 ml. of water, precooled to 5° C. The organic layer was separated, washed 2×500 ml. of cold water, dried over MgSO4, filtered and evaporated in vacuo to yield title product as a light yellow oil [190 g.; 85%; 1H--NMR (CDCl3) delta (ppm): 2.9 (s, 3H), 5.2 (s, 2H), 7.4 (m, 5H); Rf 0.75 (CH2Cl 2)]. This product was refrigerated until used in the next step. maintaining the temperature between -5° and 2° C After stirring for 10 minutes at 0°-2° C. the reaction was diluted with 500 ml precooled to 5° C The organic layer was separated washed 2×500 ml of cold water, dried over MgSO4 filtered evaporated in vacuo

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen methylene chloride (1.4 liter), benzyl alcohol (129.6 g., 1.2 moles) and triethylamine (182 g., 1.8 moles) were combined, stirred and cooled to -5° C. in an ice-water-acetone bath. A solution of methanesulfonyl chloride (150 g., 1.31 moles) in 100 ml. of methylene chloride was added over 49 minutes, maintaining the temperature between -5° and 2° C. After stirring for 10 minutes at 0°-2° C., the reaction was diluted with 500 ml. of water, precooled to 5° C. The organic layer was separated, washed 2x 500 ml. of cold water, dried over MgSO4, filtered and evaporated in vacuo to yield title product as a light yellow oil [190 g.; 85%; 1H-NMR (CDCl3) delta (ppm): 2.9 (s, 3H), 5.2 (s, 2H), 7.4 (m, 5H); Rf 0.75 (CH2Cl2)]. This product was refrigerated until used in the next step. maintaining the temperature between -5° and 2° C After stirring for 10 minutes at 0°-2° C. the reaction was diluted with 500 ml precooled to 5° C The organic layer was separated washed 2x 500 ml of cold water, dried over MgSO4 filtered evaporated in vacuo