N-butylmethanesulfonamide

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

Procedure: n-Butyllithium (4.48 ml., 11.2 mmole, 2.8 eq., 2.5M in hexane) was added to a solution of N-butylmethanesulfonamide [846 mg., 5.6 mmole, 1.4 eq., prepared as described in Example 1(a)] in tetrahydrofuran (16 ml., 0.35M) at -40° and stirred for 10 minutes. The reaction was then warmed to 0°, stirred for 30 minutes and cooled to -40°. (4S-trans)-4-(Cyclohexylmethyl)-2,2-dimethyl-5-(1-oxopentyl)-3-oxazolidinecarboxylic acid, 1,1-dimethylethyl ester (1.5 g., 3.93 mmole, 1 eq.) in tetrahydrofuran (4 ml., 1.0M) was then added. After 90 minutes at -40°, the reaction was quenched with aqueous saturated NH4Cl, warmed to room temperature and extracted three times with ether. The organic extracts were dried (Na2SO4), filtered through MgSO4, and concentrated. The residue was chromatographed on silica gel (Merck, 80 g.) eluting with hexane:acetone (10:1) to provide 237 mg. of (4S-trans)-5-[2-[butylamino)sulfonyl]-1-butyl-1-hydroxyethyl]-4-(cyclohexylmethyl)-2,2-dimethyl-3-oxazolidinecarboxylic acid, 1,1-dimethylethyl ester, isomer A; [α]D =+4.2° (c=1.0, methanol) and 101 mg. of isomer B; m.p. 138°-140°; [α]D =+5.5° (c=1.0, methanol) and 1.518 g. of a mixture of isomer A and isomer B. The reaction was then warmed to 0° stirred for 30 minutes cooled to -40° After 90 minutes at -40° the reaction was quenched with aqueous saturated NH4Cl extracted three times with ether The organic extracts were dried (Na2SO4) filtered through MgSO4 concentrated The residue was chromatographed on silica gel (Merck, 80 g.) eluting with hexane:acetone (10:1) to provide 237 mg of a mixture of isomer A and isomer B

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

Procedure: n-Butyllithium (4.48 ml., 11.2 mmole, 2.8 eq., 2.5M in hexane) was added to a solution of N-butylmethanesulfonamide [846 mg., 5.6 mmole, 1.4 eq., prepared as described in Example 1(a)] in tetrahydrofuran (16 ml., 0.35M) at -40° and stirred for 10 minutes. The reaction was then warmed to 0°, stirred for 30 minutes and cooled to -40°. (4S-trans)-4-(Cyclohexylmethyl)-2,2-dimethyl-5-(1-oxopentyl)-3-oxazolidinecarboxylic acid, 1,1-dimethylethyl ester (1.5 g., 3.93 mmole, 1 eq.) in tetrahydrofuran (4 ml., 1.0M) was then added. After 90 minutes at -40°, the reaction was quenched with aqueous saturated NH4Cl, warmed to room temperature and extracted three times with ether. The organic extracts were dried (Na2SO4), filtered through MgSO4, and concentrated. The residue was chromatographed on silica gel (Merck, 80 g.) eluting with hexane:acetone (10:1) to provide 237 mg. of (4S-trans)-5-[2-[butylamino)sulfonyl]-1-butyl-1-hydroxyethyl]-4-(cyclohexylmethyl)-2,2-dimethyl-3-oxazolidinecarboxylic acid, 1,1-dimethylethyl ester, isomer A; [α]D =+4.2° (c=1.0, methanol) and 101 mg. of isomer B; m.p. 138°-140°; [α]D =+5.5° (c=1.0, methanol) and 1.518 g. of a mixture of isomer A and isomer B. The reaction was then warmed to 0° stirred for 30 minutes cooled to -40° After 90 minutes at -40° the reaction was quenched with aqueous saturated NH4Cl extracted three times with ether The organic extracts were dried (Na2SO4) filtered through MgSO4 concentrated The residue was chromatographed on silica gel (Merck, 80 g.) eluting with hexane:acetone (10:1) to provide 237 mg of a mixture of isomer A and isomer B

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

Procedure: Methanesulfonyl chloride (6.76 ml., 87.3 mmole, 1.0 eq.) was dissolved in distilled dichloromethane (44 ml., 0.5M). The solution was cooled in an ice bath and treated dropwise with n-butylamine (17.3 ml., 175 mmole, 2.0 eq.). After the addition was complete, the clear solution was stirred overnight at room temperature. The mixture was diluted with chloroform (200 ml.), dried, washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.), dried (MgSO4) and freed of solvent in vacuo leaving an oil. This was purified by distillation to give N-butylmethanesulfonamide (11.4 g., 86%,. b.p. 106°-110°/0.5 mm) which solidified on standing. The solution was cooled in an ice bath After the addition dried washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.) dried (MgSO4) leaving an oil This was purified by distillation

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

Procedure: Methanesulfonyl chloride (6.76 ml., 87.3 mmole, 1.0 eq.) was dissolved in distilled dichloromethane (44 ml., 0.5M). The solution was cooled in an ice bath and treated dropwise with n-butylamine (17.3 ml., 175 mmole, 2.0 eq.). After the addition was complete, the clear solution was stirred overnight at room temperature. The mixture was diluted with chloroform (200 ml.), dried, washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.), dried (MgSO4) and freed of solvent in vacuo leaving an oil. This was purified by distillation to give N-butylmethanesulfonamide (11.4 g., 86%,. b.p. 106°-110°/0.5 mm) which solidified on standing. The solution was cooled in an ice bath After the addition dried washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.) dried (MgSO4) leaving an oil This was purified by distillation

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

Procedure: Methanesulfonyl chloride (6.76 ml., 87.3 mmole, 1.0 eq.) was dissolved in distilled dichloromethane (44 ml., 0.5M). The solution was cooled in an ice bath and treated dropwise with n-butylamine (17.3 ml., 175 mmole, 2.0 eq.). After the addition was complete, the clear solution was stirred overnight at room temperature. The mixture was diluted with chloroform (200 ml.), dried, washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.), dried (MgSO4) and freed of solvent in vacuo leaving an oil. This was purified by distillation to give N-butylmethanesulfonamide (11.4 g., 86%, b.p. 106°-110°/0.5 mm) which solidified on standing. The solution was cooled in an ice bath After the addition dried washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.) dried (MgSO4) leaving an oil This was purified by distillation

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

Procedure: Methanesulfonyl chloride (6.76 ml., 87.3 mmole, 1.0 eq.) was dissolved in distilled dichloromethane (44 ml., 0.5M). The solution was cooled in an ice bath and treated dropwise with n-butylamine (17.3 ml., 175 mmole, 2.0 eq.). After the addition was complete, the clear solution was stirred overnight at room temperature. The mixture was diluted with chloroform (200 ml.), dried, washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.), dried (MgSO4) and freed of solvent in vacuo leaving an oil. This was purified by distillation to give N-butylmethanesulfonamide (11.4 g., 86%, b.p. 106°-110°/0.5 mm) which solidified on standing. The solution was cooled in an ice bath After the addition dried washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.) dried (MgSO4) leaving an oil This was purified by distillation

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

Procedure: n-Butyllithium (4.48 ml., 11.2 mmole, 2.8 eq., 2.5M in hexane) was added to a solution of N-butylmethanesulfonamide [846 mg., 5.6 mmole, 1.4 eq., prepared as described in Example 1(a)] in tetrahydrofuran (16 ml., 0.35M) at -40° and stirred for 10 minutes. The reaction was then warmed to 0°, stirred for 30 minutes and cooled to -40°. (4S-trans)-4-(Cyclohexylmethyl)-2,2-dimethyl-5-(1-oxopentyl)-3-oxazolidinecarboxylic acid, 1,1-dimethylethyl ester (1.5 g., 3.93 mmole, 1 eq.) in tetrahydrofuran (4 ml., 1.0M) was then added. After 90 minutes at -40°, the reaction was quenched with aqueous saturated NH4Cl, warmed to room temperature and extracted three times with ether. The organic extracts were dried (Na2SO4), filtered through MgSO4, and concentrated. The residue was chromatographed on silica gel (Merck, 80 g.) eluting with hexane:acetone (10:1) to provide 237 mg. of (4S-trans)-5-[2-[butylamino)sulfonyl]-1-butyl-1-hydroxyethyl]-4-(cyclohexylmethyl)-2,2-dimethyl-3-oxazolidinecarboxylic acid, 1,1-dimethylethyl ester, isomer A; [α]D =+4.2° (c=1.0, methanol) and 101 mg. of isomer B; m.p. 138°-140°; [α]D =+5.5° (c=1.0, methanol) and 1.518 g. of a mixture of isomer A and isomer B. The reaction was then warmed to 0° stirred for 30 minutes cooled to -40° After 90 minutes at -40° the reaction was quenched with aqueous saturated NH4Cl extracted three times with ether The organic extracts were dried (Na2SO4) filtered through MgSO4 concentrated The residue was chromatographed on silica gel (Merck, 80 g.) eluting with hexane:acetone (10:1) to provide 237 mg of a mixture of isomer A and isomer B

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

Procedure: Methanesulfonyl chloride (6.76 ml., 87.3 mmole, 1.0 eq.) was dissolved in distilled dichloromethane (44 ml., 0.5M). The solution was cooled in an ice bath and treated dropwise with n-butylamine (17.3 ml., 175 mmole, 2.0 eq.). After the addition was complete, the clear solution was stirred overnight at room temperature. The mixture was diluted with chloroform (200 ml.), dried, washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.), dried (MgSO4) and freed of solvent in vacuo leaving an oil. This was purified by distillation to give N-butylmethanesulfonamide (11.4 g., 86%,. b.p. 106°-110°/0.5 mm) which solidified on standing. The solution was cooled in an ice bath After the addition dried washed with 0.5N HCl (2×200 ml.) and saturated NaCl solution (200 ml.) dried (MgSO4) leaving an oil This was purified by distillation