反应详情

1-Acetylpiperazine (0.164 g 1.28 mmol)was dissolved in 5 mL DCE and the resulting solution was added to 2-chloro-3-fluoro-pyridine-4-carbaldehyde (14-2, 0.170 g, 1.07 mmol). NaBH(OAc)3 (0.248 g, 1.17 mmol) was added followed by the addition of 0.100 mL of HOAc. After 45 min the reaction was quenched with sat NaHCOC3 (aq). The mixture was extracted 3× with DCM, and the organic extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (10 g column, DCM (for 4 min) gradient to 95:5 DCM/MeOH (over 8 min)), desired comes off shortly after 95:5 is attained (13 min) affording good separation from close peak preceeding desired. Afforded pure titled compound. 1H NMR (CDCl3) δ8.18 (d, 1H, J=4.9 Hz), 7.38 (t, 1H, J=4.6 Hz), 3.66 (m, 4H), 3.50 -3.48 (m, 2H), 2.50-2.46 (m, 4H), 2.09 (s, 3H).

1. customAfter 45 min the reaction was quenched with sat NaHCOC3 (aq)
2. extractionThe mixture was extracted 3× with DCM
3. dry with materialthe organic extracts were dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by flash column chromatography (10 g column, DCM (for 4 min) gradient to 95:5 DCM/MeOH (over 8 min))
7. custom(13 min)
8. customaffording good
9. customseparation
10. customfrom close peak