Dimethylformamide → 5,6,7,8-Tetrahydroimidazo[1,5-a]pyridine-3-carbaldehyde

Temperature

-78 °C

To a solution of 5,6,7,8-tetrahydro-imidazo[1,5-a]pyridine (prepared as described by Lattrell, R. et al. The J. of Antibiotics 1988, 41, 1395-1408) in THF (7 mL) at −78° C. was added a solution of n-BuLi (2.5 M in hexanes, 0.70 mL, 1.75 mmol) and the reaction stirred at −78° C. for 10 min. DMF (1.0 mL) was added to the mixture at −78° C. and the reaction warmed to room temperature and stirred for 2 h before quenching with saturated aqueous NH4Cl (5 mL). The mixture was diluted with EtOAc (30 mL) and brine and the organic phase washed with brine (1×30 mL), dried (Na2SO4) and concentrated in vacuo. The resultant brown oil (191 mg) was purified by column chromatography on silica gel (CH2Cl2/MeOH, 96:4) to afford the desired aldehyde (105 mg, 40%) as an orange oil. 1H NMR (CDCl3) δ 1.83-1.89 (m, 2H), 1.94-2.02 (m, 2H), 2.85 (t, 2H, J=6 Hz), 4.39 (t, 2H, J=6 Hz), 7.05 (s, 1H), 9.71 (s, 1H).

1. temperaturethe reaction warmed to room temperature
2. stirringstirred for 2 h
3. custombefore quenching with saturated aqueous NH4Cl (5 mL)
4. additionThe mixture was diluted with EtOAc (30 mL) and brine
5. washthe organic phase washed with brine (1×30 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated in vacuo
8. customThe resultant brown oil (191 mg) was purified by column chromatography on silica gel (CH2Cl2/MeOH, 96:4)

ORD record

ord-786b9c249db74b82bf36d999766318b3

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07354932B2