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

HRID 928210

Reaction equation

HRID 928210 reaction equation
[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][C:10]([F:15])(F)[C:9]1=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[F-].CO[CH2:21][N:22]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:23][Si](C)(C)C>C(#N)C>[CH2:1]([N:8]1[C:9](=[O:16])[C@:10]2([F:15])[C@@H:11]([CH2:21][N:22]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:23]2)[C:12]1=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 224478Lithium fluoride2×HCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 114815201-Benzyl-3,3-difluoropyrrolidine-2,5-dione

Product 1

HCID 131735057(+/-)-cis-2,5-dibenzyl-3a-fluorotetrahydropyrrolo[3,4-c]pyrrole-1,3(2H,3aH)-dione

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-682af41dad7142ed9d919f31d9f67340
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Linked notes

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