Ammonium Chloride → 2-(5-chloro-4-(1-(4-chloro-2-methylphenyl)-2-methoxyvinyl)-1-methyl-1H-pyrazol-3-yl)pyridine

Temperature

-10 °C

To a solution of (methoxymethyl)triphenylphosphonium chloride (91 g, 265 mmol) in THF (330 mL) at about −10° C. was added 1.6 M butyllithium in hexanes (161 mL, 258 mmol) dropwise. The mixture was stirred at about −10° C. for about 1 h. A solution of (5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)(4-chloro-2-methylphenyl)methanone (22.35 g, 64.6 mmol) in THF (220 mL) was added to the mixture in a dropwise manner. The mixture was stirred at about −10° C. for about 16 h then treated with a saturated aqueous NH4Cl solution (1000 mL). The mixture was extracted with EtOAc (2×700 mL). The combined organic layers were washed with brine (500 mL), dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, 0-25% EtOAc/heptanes) to give 2-(5-chloro-4-(1-(4-chloro-2-methylphenyl)-2-methoxyvinyl)-1-methyl-1H-pyrazol-3-yl)pyridine (16.65 g, 69%): LC-MS (Table 1, Method g) Rt=2.56 min, m/z 374/376 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 8.44-8.39 (m, 1H), 7.70-7.58 (m, 2H), 7.21-6.93 (m, 4H), 6.39 (s, 1H), 3.90 (s, 3H), 3.64 (s, 3H), 2.28 (2s, 3H) major; 1H-NMR (CDCl3, Bruker 400 MHz) δ 8.44-8.39 (m, 1H), 7.70-7.58 (m, 2H), 7.21-6.93 (m, 4H), 6.38 (s, 1H), 3.88 (s, 3H), 3.52 (s, 3H), 2.20 (s, 3H) minor.

1. stirringThe mixture was stirred at about −10° C. for about 16 h
2. extractionThe mixture was extracted with EtOAc (2×700 mL)
3. washThe combined organic layers were washed with brine (500 mL)
4. dry with materialdried with Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography (SiO2, 0-25% EtOAc/heptanes)

ORD record

ord-50d8b65fd1084da6bcc9b3a0defa808f

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150592B2