Potassium Carbonate → 3-(4-Pyridinylthio)aniline

To a solution of 3-aminothiophenol (3.8 mL, 34 mmoles) in anh DMF (90 mL) was added 4-chloropyridine hydrochloride (5.4 g, 35.6 mmoles) followed by K2CO3 (16.7 g, 121 mmoles). The reaction mixture was stirred at room temp. for 1.5 h, then diluted with EtOAc (100 mL) and water (100 mL). The aqueous layer was back-extracted with EtOAc (2×100 mL). The combined organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure. The residue was filtered through a pad of silica (gradient from 50% EtOAc/50% hexane to 70% EtOAc/30% hexane) and the resulting material was triturated with a Et2O/hexane solution to afford the desired product (4.6 g, 66%): TLC (100% ethyl acetate) Rf 0.29; 1H-NMR (DMSO-d6) δ 5.41 (s, 2H), 6.64-6.74 (m, 3H), 7.01 (d, J=4.8, 2H), 7.14 (t, J=7.8 Hz, 1H), 8.32 (d, J=4.8, 2H). A14b. General Method for Substituted Aniline Synthesis via Nucleophilic Aromatic Substitution using a Halopyridine

1. extractionThe aqueous layer was back-extracted with EtOAc (2×100 mL)
2. washThe combined organic layers were washed with a saturated NaCl solution (100 mL)
3. dry with materialdried (MgSO4)
4. concentrationconcentrated under reduced pressure
5. filtrationThe residue was filtered through a pad of silica (gradient from 50% EtOAc/50% hexane to 70% EtOAc/30% hexane)
6. customthe resulting material was triturated with a Et2O/hexane solution

ORD record

ord-28785750a1e349149a955798f088d56e

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07517880B2