Hydrochloric Acid → 1'-{[1-(2,4-Dichlorophenyl)cyclopropyl]carbonyl}-3H-spiro[furo[3,4-c]pyridin e-1,3'-pyrrolidin]-3-one

Temperature

-55 °C

To a solution of 2,2,6,6-tetramethyl-piperidine, (1.18 mL, 0.00700 mol) in tetrahydrofuran (30 mL, 0.4 mol) at −78° C. was added n-butyllithium in hexane (2.5 M, 3.7 mL). After stirring for 15 min, a suspension of niacin (0.287 g, 0.00233 mol) in THF was added and the mixture was stirred at −78° C. for 10 min. The reaction mixture was then warmed to −55° C. for 60 min. A solution of 1-{[1-(2,4-dichlorophenyl)cyclopropyl]carbonyl}pyrrolidin-3-one (580 mg, 0.0019 mol) in THF (2 mL) was added to the above mixture and stirring was continued at −55 degrees celsius for 20 min. The reaction mixture was then allowed to warm to rt for 1 h and then acidified (pH ˜1) using 6M HCl aq. solution. The reaction mixture was stirred at rt overnight and then neutralized (pH ˜7). The product from the mixture was extracted with AcOEt. The organic extract was washed with brine, dried with MgSO4, and concentrated in-vane. The crude product was purified by Combiflash followed by separation of the enantiomers using a chrial column. LCMS: m/z 402.0 & 404.0 (M+H)+.

1. additionwas added
2. stirringthe mixture was stirred at −78° C. for 10 min
3. stirringstirring
4. waitwas continued at −55 degrees celsius for 20 min
5. temperatureto warm to rt for 1 h
6. stirringThe reaction mixture was stirred at rt overnight
7. extractionThe product from the mixture was extracted with AcOEt
8. extractionThe organic extract
9. washwas washed with brine
10. dry with materialdried with MgSO4
11. concentrationconcentrated in-vane
12. customThe crude product was purified by Combiflash
13. customfollowed by separation of the enantiomers

ORD record

ord-a349c0b58a39452a98ed51617ea977f1

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09126927B2