tert-butyl N-(3-formylpyridin-2-yl)carbamate → [3-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzene sulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-pyridin-2-yl]-carbamic acid tert-butyl ester

Temperatur

0 °C

To a solution of N-(2-bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (3.27 g, 6.64 mmol) in THF (20 mL) under nitrogen atmosphere at 0° C. was added dropwise isopropylmagnesium chloride (2 M solution in THF, 6.62 mL, 13.25 mmol). The mixture was then stirred for 30 min at 0° C. followed by the addition of a solution of (3-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (590 mg, 2.65 mmol) in THF (3 mL) at 0° C. The mixture was stirred at room temperature for 3 hours, quenched with saturated aqueous NH4Cl solution (10 mL) and extracted with EtOAc (2×50 mL). Combined organic layers were washed with saturated aqueous NH4Cl solution (50 mL), brine (50 mL), dried (anhydrous Na2SO4) and concentrated under reduced pressure. Obtained residue was column purified (SiO2, 50% EtOAc-hexanes) to obtain [3-({5-chloro-3-[(4-chloro-3-trifluoromethyl-benzene sulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-pyridin-2-yl]-carbamic acid tert-butyl ester (750 mg) in 44% yield as yellow solid. ESMS m/z (relative intensity): 637 (M+H)+ (100).

1. stirringThe mixture was stirred at room temperature for 3 hours
2. customquenched with saturated aqueous NH4Cl solution (10 mL)
3. extractionextracted with EtOAc (2×50 mL)
4. washCombined organic layers were washed with saturated aqueous NH4Cl solution (50 mL), brine (50 mL)
5. dry with materialdried (anhydrous Na2SO4)
6. concentrationconcentrated under reduced pressure
7. custompurified (SiO2, 50% EtOAc-hexanes)

ORD-Eintrag

ord-ee3f094c873547ab9a8e8a6e1e3294b8

Quelldatensatz

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07622583B2