Methylamine → (3-(3-Pyridyloxy)propyl)methylamine

Temperature

80 °C

The 3-chloro-1-(3-pyridyloxy)propane (4.90 g, 28.55 mmol) was dissolved in methanol (60 mL) and added to a 40 wt % solution of methylamine (60 mL) in a heavy-walled pressure-tube apparatus. The tube was sealed and the mixture was stirred and heated at 80° C. for 15 h. After cooling, the mixture was concentrated by rotary evaporation, a saturated NaCl solution (25 mL) was added, and the mixture was basified with 20% NaOH solution (5.0 mL). The mixture was extracted with chloroform (4×30 mL). The combined chloroform extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to give 3.64 g of a brown oil. The product was purified by column chromatography on silica gel (100 g) eluting with chloroform-methanol-triethylamine (70:30:2.5, v/v/v). Selected fractions containing the product (Rf 0.30) were combined and concentrated by rotary evaporation. The resulting residue was dissolved in chloroform (15 mL), dried (Na2SO4), filtered, and concentrated by rotary evaporation to give 1.92 g (40.4%) of a brown oil. 1H NMR (CDCl3, 300 MHz): δ8.31 (dd, 1H, J=2.39, 1.44 Hz), 8.20 (dd, 1H, J=3.88, 2.29 Hz), 7.14 (m, 2H, J=3.90, 1.11 Hz), 4.09 (t, 2H, J=6.22 Hz), 2.78 (t, 2H, J=6.80 Hz), 2.46 (s, 3H), 1.99 (p, 2H, J=6.54 Hz), 1.59 (br, s, 1H). 13C NMR (CDCl3, 75 MHz): δ155.16, 142.08, 138.09, 123.84, 121.05, 66.59, 48.78, 36.53, 29.44. EI-MS: m/z (relative intensity) 166 (M+, 10.08%), 123 (41.85%), 95 (100.00%), 70 (45.84%), 44 (89.75%), 39 (41.62%).

1. customThe tube was sealed
2. temperatureAfter cooling
3. concentrationthe mixture was concentrated by rotary evaporation
4. additiona saturated NaCl solution (25 mL) was added
5. extractionThe mixture was extracted with chloroform (4×30 mL)
6. dry with materialThe combined chloroform extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated by rotary evaporation

ORD record

ord-cef8457852fb4637aceec7b1963f338b

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06441007B1