Methylamine → HCID 10198746, compound

Temperature

102 °C

Crude 3-bromo-5-(3-chloropropoxy)pyridine (4.07 g) from the previous step was dissolved in CH3OH (28 mL) and added to a 40 wt % solution of methylamine (35 mL) in a heavy-walled pressure-tube apparatus. The tube was sealed and the mixture was stirred and heated at 102° C. for 4 h. After cooling, the solution was concentrated by rotary evaporation, a saturated NaCl solution (15 mL) was added, and the mixture was basified with 10% NaOH solution (5 mL). The mixture was extracted with CHCL3 (4×30 mL). The combined CHCL3 extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to give 2.07 g of a brown oil. The product was purified by column chromatography on silica gel (100 g) eluting with CHCL3 --CH3OH (9:1, v/v) to remove impurities, followed by CHCL3 --CH3OH--Et3N (75:25:2, v/v/v) to collect the product. Selected fractions containing the product (Rf 0.13) were combined and concentrated by rotary evaporation. The resulting brown oil was dissolved in CHCL3 (25 mL), dried (Na2SO4), filtered, and concentrated by rotary evaporation to give 0.79 g (29.5% based upon 5-bromo-3-hydroxypyridine) of an amber-brown oil, which tended to crystallize as light amber crystals. 1H NMR (CDCl3, 300 MHz): δ 8.27 (d, 1H, J=1.85 Hz), 8.24 (d, 1 H, J=2.48 Hz), 7.38 (dd, 1H, J=1.91, 1.91 Hz), 4.09 (t, 2H, J=6.22 Hz), 2.78 (t, 2H, J=6.84 Hz), 2.47 (s, 3H), 1.99 (p, 2H, J=6.56 Hz), 1.53 (br s, 1H).

1. customThe tube was sealed
2. temperatureAfter cooling
3. concentrationthe solution was concentrated by rotary evaporation
4. additiona saturated NaCl solution (15 mL) was added
5. extractionThe mixture was extracted with CHCL3 (4×30 mL)
6. dry with materialwere dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated by rotary evaporation

ORD record

ord-7b2b3d021ccc4e7d93f1a51cd54b4f91

Source dataset

uspto-grants-2000_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06166047