methanesulfonyl bromide

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

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

Procedure: To a solution of 3-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-indol-3-yl]propan-1-ol (Intermediate 41; 3.2 g, 0.009 mol) in CH2Cl2 (25 mL) was added at −40° C. methanesulfonyl bromide (0.93 mL, 0.011 mol) and triethylamine (1.74 mL, 0.012 mol). The reaction mixture was stirred for 5 minutes. More CH2Cl2 was added into the mixture and the organic layer was washed with water. The solvent was removed under reduced pressure giving the title compound (3.5 g, 88%), which was used in the next step without further purification. the organic layer was washed with water The solvent was removed under reduced pressure

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

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

Procedure: Methylsulfonyl bromide (0.96 mL) is added to a solution of {(S)-6-[(R)-4-hydroxymethyl-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester (2.00 g) and triethylamine (1.98 mL) in dichloromethane (20 mL) chilled in an ice bath. The cooling bath is removed, and the solution is stirred at room temperature overnight. More dichloromethane is added, and the resulting solution is washed with aqueous NaHCO3 solution and brine, dried (Na2SO4), and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate) to give the title compound. LC (method 2): tR=1.24 min. chilled in an ice bath The cooling bath is removed More dichloromethane is added the resulting solution is washed with aqueous NaHCO3 solution and brine dried (Na2SO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate)

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

Procedure: Methylsulfonyl bromide (0.96 mL) is added to a solution of {(S)-6-[(R)-4-hydroxymethyl-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester (2.00 g) and triethylamine (1.98 mL) in dichloromethane (20 mL) chilled in an ice bath. The cooling bath is removed, and the solution is stirred at room temperature overnight. More dichloromethane is added, and the resulting solution is washed with aqueous NaHCO3 solution and brine, dried (Na2SO4), and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate) to give the title compound. LC (method 2): tR=1.24 min. chilled in an ice bath The cooling bath is removed More dichloromethane is added the resulting solution is washed with aqueous NaHCO3 solution and brine dried (Na2SO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate)

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

Procedure: 130 mg of zinc chloride, 3.2 g (20 mmoles) of methanesulfonic acid bromide and 0.15 ml of 50% strength hydrogen peroxide are successively added to a solution of 2.1 g (20 mmoles) of styrene in 5 ml of nitromethane. After 50 hours at room temperature, the mixture is taken up in methylene chloride and the solution is washed with water. The crude 1-methylsulfonyl-2-bromo-2-phenylethane which remains after stripping off the methylene chloride is dissolved in 10 ml of benzene and dehydrobrominated by adding 25 mmoles of triethylamine. Distillation at from 121° to 124° C. at 0.01 mm Hg gives β-methylsulfonylstyrene, of melting point 77° - 79° C. (after recrystallization from ether). According to the NMR spectrum (J = 15.5 Hz), the product is in the trans-configuration. the solution is washed with water is dissolved in 10 ml of benzene Distillation at from 121° to 124° C. at 0.01 mm Hg

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of mesyl bromide (17.23 mmol) in 10 mL of THF cooled to −78° C. was added a 1.7 M THF solution of tBuLi (34.5 mmol) dropwise. The mixture was left stirring at −78° C. for 1 h. The mixture was then allowed to reach 0° C. and a solution of 2-methoxyquinoline (12.9 mmol) in THF (40 mL) was added dropwise over 10 min. The resulting mixture was aged at 0° C. for 1 h, cooled to −78° C. and added dropwise with a solution of tert-butyl(2-(methoxy(methyl)amino)-2-oxoethyl)carbamate (4.31 mmol) in 20 mL of THF. The mixture was stirred at −78° C. for 30 min then left at room temperature over night. The mixture was diluted with DCM and washed with sat. aq. NaHCO3, dried (Na2SO4), concentrated under reduced pressure and the crude product was purified by flash chromatography (SiO2, Petroleum ether/EtOAc, from 5% to 40% EtOAc). Pooled fractions were concentrated under vacuum to title product (1.01 g). MS (ES) C17H20N2O4 requires: 316.35, found: 317. The mixture was left to reach 0° C. The resulting mixture was aged at 0° C. for 1 h cooled to −78° C. The mixture was stirred at −78° C. for 30 min then left at room temperature over night washed with sat. aq. NaHCO3 dried (Na2SO4) concentrated under reduced pressure the crude product was purified by flash chromatography (SiO2, Petroleum ether/EtOAc, from 5% to 40% EtOAc) Pooled fractions were concentrated under vacuum to title product (1.01 g)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of mesyl bromide (17.23 mmol) in 10 mL of THF cooled to −78° C. was added a 1.7 M THF solution of tBuLi (34.5 mmol) dropwise. The mixture was left stirring at −78° C. for 1 h. The mixture was then allowed to reach 0° C. and a solution of 2-methoxyquinoline (12.9 mmol) in THF (40 mL) was added dropwise over 10 min. The resulting mixture was aged at 0° C. for 1 h, cooled to −78° C. and added dropwise with a solution of tert-butyl(2-(methoxy(methyl)amino)-2-oxoethyl)carbamate (4.31 mmol) in 20 mL of THF. The mixture was stirred at −78° C. for 30 min then left at room temperature over night. The mixture was diluted with DCM and washed with sat. aq. NaHCO3, dried (Na2SO4), concentrated under reduced pressure and the crude product was purified by flash chromatography (SiO2, Petroleum ether/EtOAc, from 5% to 40% EtOAc). Pooled fractions were concentrated under vacuum to title product (1.01 g). MS (ES) C17H20N2O4 requires: 316.35, found: 317. The mixture was left to reach 0° C. The resulting mixture was aged at 0° C. for 1 h cooled to −78° C. The mixture was stirred at −78° C. for 30 min then left at room temperature over night washed with sat. aq. NaHCO3 dried (Na2SO4) concentrated under reduced pressure the crude product was purified by flash chromatography (SiO2, Petroleum ether/EtOAc, from 5% to 40% EtOAc) Pooled fractions were concentrated under vacuum to title product (1.01 g)

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

Procedure: 159 g (1 mole) of methanesulfonyl bromide are slowly added dropwise, at 45° C., to a mixture of 78 g (1.07 moles) of methyl allyl ether, 7.5 g of zinc chloride and 3.3 ml of 50% strength hydrogen peroxide. After the exothermic reaction has subsided, the mixture is stirred for a further 30 minutes and is diluted with 450 ml of benzene, and 135 g (1.33 moles) of triethylamine are added at room temperature, whilst cooling. After 2 hours, the precipitate is filtered off and the solvent is distilled off. Distillation of the residue gives 125 g of 1-methylsulfonyl-3-methoxy-prop-1-ene, boiling point 114°-115° C./0.3 mm Hg. According to the NMR spectrum, the product is a mixture of cis and trans isomers in the ratio of 15:85. After the exothermic reaction are added at room temperature whilst cooling After 2 hours the precipitate is filtered off the solvent is distilled off Distillation of the residue

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

Procedure: Methylsulfonyl bromide (0.96 mL) is added to a solution of {(S)-6-[(R)-4-hydroxymethyl-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester (2.00 g) and triethylamine (1.98 mL) in dichloromethane (20 mL) chilled in an ice bath. The cooling bath is removed, and the solution is stirred at room temperature overnight. More dichloromethane is added, and the resulting solution is washed with aqueous NaHCO3 solution and brine, dried (Na2SO4), and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate) to give the title compound. LC (method 4): tR=1.24 min. chilled in an ice bath The cooling bath is removed More dichloromethane is added the resulting solution is washed with aqueous NaHCO3 solution and brine dried (Na2SO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate)

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

Procedure: To a solution of 3-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-indol-3-yl]propan-1-ol (Intermediate 41; 3.2 g, 0.009 mol) in CH2Cl2 (25 mL) was added at −40° C. methanesulfonyl bromide (0.93 mL, 0.011 mol) and triethylamine (1.74 mL, 0.012 mol). The reaction mixture was stirred for 5 minutes. More CH2Cl2 was added into the mixture and the organic layer was washed with water. The solvent was removed under reduced pressure giving the title compound (3.5 g, 88%), which was used in the next step without further purification. the organic layer was washed with water The solvent was removed under reduced pressure