Hydrochloric Acid → 8-(Benzyloxy)imidazo[1,2-a]pyridine

Temperature

55 °C

As shown in FIG. 6, concentrated HCl (34 mL, 345 mmol) was added drop-wise to 2-bromo-1,1-diethoxyethane 17 (29.56, 150 mmol) at room temperature in a 250-mL three neck round bottomed flask. The mixture was then heated at 55° C. for 30 minutes. The pale yellow mixture was then cooled to 0° C. and anhydrous Na2SO4 (64 g) added and the reaction stirred for 1.0 hour. The reaction mixture now containing crude bromoacetaldehyde 18 was filtered into a three neck 1000-mL round bottomed flask and the cake washed with ethanol (100 mL). The flask was then cooled to 0° C. and 2- amino-3-benzyloxypyridine 19 (10.0 g, 50 mmol) added portion wise followed by the addition of NaHCO3 (42 g, 500 mmol). There was evolution of gas. After the bubbling had ceased, the mixture was refluxed at 70° C. for 1.0 hour. The reaction mixture was then cooled to room temperature, filtered and concentrated under reduced pressure. CH2Cl2 was added to the residue at 0° C. and 40% NaOH (30 mL) added to pH 10. The mixture was then diluted with water (100 mL) and the organic phase separated, dried (Na2SO4) and concentrated under reduced pressure. Purification on silica gel (CombiFlash, Heptanes/EtOAc elution) afforded 8-benzyloxy-imidazo[1,2-α]pyridine 24 as colorless needles. 7.2 g, 64%, yield.

1. temperatureThe pale yellow mixture was then cooled to 0° C.
2. filtrationwas filtered into a three neck 1000-mL round bottomed flask
3. washthe cake washed with ethanol (100 mL)
4. temperatureThe flask was then cooled to 0° C.
5. temperaturethe mixture was refluxed at 70° C. for 1.0 hour
6. temperatureThe reaction mixture was then cooled to room temperature
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. additionCH2Cl2 was added to the residue at 0° C.
10. addition40% NaOH (30 mL) added to pH 10
11. additionThe mixture was then diluted with water (100 mL)
12. customthe organic phase separated
13. dry with materialdried (Na2SO4)
14. concentrationconcentrated under reduced pressure
15. customPurification on silica gel (CombiFlash, Heptanes/EtOAc elution)

ORD record

ord-5bc0db2dcf314032bd6780e792b65d8b

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618079B2