Formic Acid → 3-Bromo-5-(1-methyl-pyrrolidin-2-yl)-pyridine

Temperatur

80 °C

Enantiomerically enriched 5-bromo-3-(2-pyrrolidinyl)pyridine (1.82 g, 8 mmol) was dissolved in a mixture of 98% formic acid (16 mL) and 37% aqueous formaldehyde (8 mL). The solution was heated with stirring for 3 h at 80° C. After cooling to 25° C. the mixture was concentrated in vacuo and water (30 mL) added. The mixture was basified with solid NaOH to pH 12 and extracted with methylene chloride (3×40 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude material was chromatographed on silica gel with ethyl acetate:hexane (1:3) as eluant to afford 5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine as an oil, 1.63 g,84%. LRMS (EI) m/e 242 (C10H13N281Br), 241 (C10 H13N279Br--+H), 240 (C10H13 N279Br), 239 (C10H13N279Br--+H); 1H NMR (DMSO-d6, 300 MHz) δ 8.55 (d, J=2.1 Hz, 1H), 8.44 (d, J=1.9 Hz, 1H), 7.88 (t, J=1.9 Hz, 1H), 3.24 (b-dt, J=8.1 Hz, 1H), 3.10 (t, J=8.0 Hz, 1H), 2.36 (m, 1H), 2.18 (s, 3H), 1.95 (m, 1H), 1.85 (m, 1H), 1.70 (m, 1H).

1. temperatureThe solution was heated
2. temperatureAfter cooling to 25° C. the mixture
3. concentrationwas concentrated in vacuo and water (30 mL)
4. additionadded
5. extractionextracted with methylene chloride (3×40 mL)
6. washThe combined organic extracts were washed with brine (20 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customThe crude material was chromatographed on silica gel with ethyl acetate:hexane (1:3) as eluant

ORD-Eintrag

ord-a2b26e29729f4281a22734f1fca92c45

Quelldatensatz

uspto-grants-1997_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05677459