2,4-Dimethylnicotinaldehyde → N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

Temperature

0 °C

To a solution of N-(2-bromo-5-methyl-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (500 mg, 1.06 mmol) in THF (3 mL) under nitrogen atmosphere at −30° C. was added drop wise isopropylmagnesium chloride (2 M solution in THF, 1.27 mL, 2.54 mmol). The mixture was then stirred for 30 min at 0° C. followed by the addition of a solution of 2,4-dimethyl-pyridine-3-carbaldehyde (271 mg, 2.01 mmol) at −30° C. The mixture was stirred at room temperature for 3 hours, quenched with saturated aqueous NH4Cl solution (5 mL) and extracted with EtOAc (2×25 mL). Combined organic layers were washed with saturated aqueous NH4Cl solution (25 mL), brine (25 mL), dried (anhydrous Na2SO4) and concentrated under reduced pressure. Obtained residue was column purified (SiO2, 50% EtOAc-hexanes) to obtain 4-chloro-N-{2-[(2,4-dimethyl-pyridin-3-yl)-hydroxy-methyl]-5-methyl]-5-methyl-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzene sulfonamide (288 mg) as yellow foam in 51% yield. ESMS m/z (relative intensity): 530 (M+H)+ (100).

1. stirringThe mixture was stirred at room temperature for 3 hours
2. customquenched with saturated aqueous NH4Cl solution (5 mL)
3. extractionextracted with EtOAc (2×25 mL)
4. washCombined organic layers were washed with saturated aqueous NH4Cl solution (25 mL), brine (25 mL)
5. dry with materialdried (anhydrous Na2SO4)
6. concentrationconcentrated under reduced pressure
7. custompurified (SiO2, 50% EtOAc-hexanes)

ORD record

ord-3fad54a0dd474416b784614bee96c2c2

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093247B2