Lithium fluoride → (+/-)-cis-2,5-dibenzyl-3a-fluorotetrahydropyrrolo[3,4-c]pyrrole-1,3(2H,3aH)-dione

To a solution of 1-benzyl-3,3-difluoropyrrolidine-2,5-dione (325 mg, 1.44 mmol) in acetonitrile (3.6 mL), LiF (56 mg, 1.50 eq) and a stir bar were added. The reaction mixture was sonicated for 2.5 hr at rt. N-(Methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (0.4 mL, 1.59 mmol, 1.10 eq) and LiF (37 mg, 1.44 mmol, 1 eq) were added and continued to sonicate for 0.5 hr. The reaction mixture was concentrated and the salt was removed by filtration. The crude residue was purified by column chromatography and eluted with 2 to 20% EtOAc/heptane and purified further with 2 to 10% EtOAc/heptane. The desired fractions were faintly ultraviolet active but were visualized with KMNO4 stain. The title compound was isolated as a yellow oil (196 mg, 40% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.10-7.43 (m, 10 H) 4.57-4.75 (m, 2 H) 3.63 (s, 2 H) 3.56-3.65 (m, 1 H) 3.33-3.41 (m, 1 H) 3.13 (d, J=9.29 Hz, 1 H) 2.74 (dd, J=9.35, 7.03 Hz, 1 H) 2.57-2.70 (m, 1 H). m/z (APCI+) for C20H20FN2O2 339.20 (M+H)+.

1. customThe reaction mixture was sonicated for 2.5 hr at rt
2. customto sonicate for 0.5 hr
3. concentrationThe reaction mixture was concentrated
4. customthe salt was removed by filtration
5. customThe crude residue was purified by column chromatography
6. washeluted with 2 to 20% EtOAc/heptane
7. custompurified further with 2 to 10% EtOAc/heptane

ORD-Eintrag

ord-682af41dad7142ed9d919f31d9f67340

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09290496B2