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

온도

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) δ8.55 (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 기록

ord-e852fe680e5a4a61bf4aebaa36a6c6c5

출처 데이터셋

uspto-grants-1997_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05703100