Sodium Carbonate → 2-[4-(Methylthio)phenyl]-4-(trifluoromethyl)-pyridine

HRID 268599Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[CH3:12][S:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[CH3:12][S:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=2)=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 2-chloro-4-(trifluoromethyl)pyridine (19.9 g, 0.11 mol), 4-(methylthio)phenylboronic acid (21.9 g, 0.13 mol), 1M aqueous sodium carbonate (180 mL) and 1,2-dimethoxyethane (270 mL) under an atmosphere of nitrogen was added palladium tetrakistriphenylphosphine (3.78 g, 3.3 mmol) and the reaction heated at 100° C. for 14 hours. After cooling and concentration in vacuo, the residue was partitioned between ethyl acetate (350 mL) and water (400 mL) and separated. The aqueous layer was further extracted with ethyl acetate (2×150 mL) and the combined organic layers were dried over sodium sulfate and concentrated in vacuo. Filtration through a pad of silica gel (200 g) eluting with a gradient of ethyl acetate in cyclohexane gave the title compound (29.4 g) LC retention time 3.62 mins, MS m/z 269 (MH+).

Workup

temperatureAfter cooling
concentrationconcentration in vacuo
customthe residue was partitioned between ethyl acetate (350 mL) and water (400 mL)
customseparated
extractionThe aqueous layer was further extracted with ethyl acetate (2×150 mL)
dry with materialthe combined organic layers were dried over sodium sulfate
concentrationconcentrated in vacuo
filtrationFiltration through a pad of silica gel (200 g)
washeluting with a gradient of ethyl acetate in cyclohexane

Sources & evidence

ORD record: ord-c885bfe0aea24d4a84062d99ee26bc68
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07446117B2

Reaction notes

Loading…