o-Methylvalerolactim → 3-(3,4-Difluorophenyl)-5,6,7,8-tetrahydroimidazo-[1,5-a]pyridine-1-carboxylic acid

Temperature

90 °C

6-methoxy-2,3,4,5-tetrahydropyridine (0.431 g, 3.80 mmol) was dissolved in THF (5 mL) in a 40 mL screw-cap vial and 2-(3,4-difluorophenyl)oxazol-5(4H)-one (0.75 g, 3.80 mmol) in THF (5 mL) was added, producing an orange solution. The vial was capped and heated to 90° C. for 3 hours. THF was removed under reduced pressure and the residue was dissolved in MeOH (10 ml) and lithium hydroxide monohydrate (0.479 g, 11.41 mmol) in water (1 mL) was added. The reaction was heated to 90° C. for 3 hours. MeOH was removed by evaporation under reduced pressure. The remaining aqueous solution was diluted with water (5 mL) and acidified to pH 2 with 5M HCl. The solution was extracted with EtOAc (3×5 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and evaporated to yield the desired product as a brown oil (742 mg, 71%) that was used without further purification. LCMS (+ESI) m/z: 279.3 [M+H]+.

1. customscrew-cap vial
2. customproducing an orange solution
3. customThe vial was capped
4. customTHF was removed under reduced pressure
5. dissolutionthe residue was dissolved in MeOH (10 ml)
6. temperatureThe reaction was heated to 90° C. for 3 hours
7. customMeOH was removed by evaporation under reduced pressure
8. additionThe remaining aqueous solution was diluted with water (5 mL)
9. extractionThe solution was extracted with EtOAc (3×5 mL)
10. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
11. filtrationfiltered
12. customevaporated

ORD record

ord-6dfdf4e4b2b14b39b3030a94bfc4e3bf

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835422B2