Isopropanol → 6,6-Dimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carbaldehyde

The mixture of 2-bromo-3-hydroxypropenal (10.1 g, 67 mmol), p-toluenesulfonic acid monohydrate (0.13 g, 0.6 mmol) and 2-propanol (12.6 mL, 165 mmol) in cyclohexane (100 mL) was azeotroped until the vaper temperature over 80° C. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in dry EtOH (200 mL). The dry EtOH (350 mL) solution of 5,5-dimethylpiperidine-2-ylideneamine monohydrochloride (9.9 g, 61 mmol) and the dry EtOH (50 mL) solution of NaOMe (28%, 11.7 g, 61 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 2 h, and then the reaction solution was removed in vacuo. The residue was dissolved in CHCl3 (300 mL) and triethylamine (8.5 mL, 61 mmol) was added, and then the reaction mixture was heated to reflux for 2 h. The reaction mixture was cooled to room temperature, and then the reaction solution was removed in vacuo. The residue was dissolved in CH2HI2 (600 mL) and washed with 50% K2CO3 aqueous solution (2×200 mL). The combined aqueous solution was extracted with CH2Cl2 (2×200 mL). The combined organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, eluted with CHCl3-methanol (50:1), and the titled compound 6,6-Dimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carbaldehyde (brown solid, 4.4 g, 40.7%) and 6,6-Dimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-3-carbaldehyde (orange solid, 1.7 g, 15.8%) were obtained.

1. customwas azeotroped until the vaper temperature over 80° C
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. dissolutionThe residue was dissolved in dry EtOH (200 mL)
4. customthe reaction solution was removed in vacuo
5. dissolutionThe residue was dissolved in CHCl3 (300 mL)
6. temperaturethe reaction mixture was heated
7. temperatureto reflux for 2 h
8. temperatureThe reaction mixture was cooled to room temperature
9. customthe reaction solution was removed in vacuo
10. dissolutionThe residue was dissolved in CH2HI2 (600 mL)
11. washwashed with 50% K2CO3 aqueous solution (2×200 mL)
12. extractionThe combined aqueous solution was extracted with CH2Cl2 (2×200 mL)
13. dry with materialThe combined organic layer was dried (MgSO4)
14. filtrationfiltered
15. concentrationThe filtrate was concentrated under reduced pressure
16. washeluted with CHCl3-methanol (50:1)

ORD 기록

ord-70c6a99a1d0b40d18c9338bbda25ea09

출처 데이터셋

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07112582B2