4-Fluorobenzaldehyde → 3-(4-Fluorobenzyl)pyrrolidin-2-one

To a suspension of potassium tert-butoxide (2.00 g, 18.0 mmol) in anhydrous tetrahydrofuran (40 mL) was added a mixture of 1-(2,2,2-trifluoroacetyl)-pyrrolidin-2-one (2.12 g, 12.0 mmol) and 4-fluorobenzaldehyde (1.24 mL, 12.0 mmol) in anhydrous tetrahydrofuran (5 mL) dropwise at 0° C. The reaction mixture was stirred at ambient temperature for 2 hours, then refluxed for 1 hour and concentrated in vacuo. Water (150 mL) was added to the residue. The white solid precipitated was filtered and re-dissolved in ethyl acetate (50 mL) and then hydrogenated in the presence of catalytic amount of palladium on carbon (20% w/w) at ambient temperature and atmospheric pressure for 3 hours. The reaction mixture was filtered through a bed of celite. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (ethyl acetate) to afford the title compound as a white solid (0.72 g, 35%): 1H NMR (300 MHz, CDCl3) δ 7.20-7.09 (m, 2H), 7.00-6.90 (m, 2H), 6.42 (s, 1H), 3.31-3.07 (m, 3H), 2.71-2.54 (m, 2H), 2.19-2.03 (m, 1H), 1.89-1.69 (m, 1H); MS (ES+) m/z 194.1 (M+1).

1. additionwas added
2. temperaturerefluxed for 1 hour
3. concentrationconcentrated in vacuo
4. additionWater (150 mL) was added to the residue
5. customThe white solid precipitated
6. filtrationwas filtered
7. dissolutionre-dissolved in ethyl acetate (50 mL)
8. customhydrogenated in the presence of catalytic amount of palladium on carbon (20% w/w) at ambient temperature
9. waitatmospheric pressure for 3 hours
10. filtrationThe reaction mixture was filtered through a bed of celite
11. concentrationThe filtrate was concentrated in vacuo
12. customthe residue was purified by column chromatography (ethyl acetate)

ORD record

ord-d44586d8fcee4403bfc2914cdeecfeca

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08236835B2