Triphenylphosphine → (R)-5-(Aminomethyl)-1-(4-fluorophenyl)pyrrolidin-2-one

HRID 1477646Notes

Reaction equation

HRID 1477646 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([CH2:13]O)[CH2:11][CH2:10][C:9]2=[O:15])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH:35](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O.N(C(OCC)=O)=NC(OCC)=O>C(#N)C.ClCCl>[NH2:35][CH2:13][C@@H:12]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:9](=[O:15])[CH2:10][CH2:11]1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 279800Di-tert-butyl IminodicarboxylateHCID 117839578HCID 117839578, compound

Product 1

HCID 96683900(R)-5-(Aminomethyl)-1-(4-fluorophenyl)pyrrolidin-2-oneYield 24.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a dichloromethane (10 mL)-acetonitrile (2.0 mL) solution of (R)-1-(4-fluorophenyl)-5-(hydroxymethyl)pyrrolidin-2-one (500 mg, 2.39 mmol) synthesized in Reference Synthesis Example 215, triphenylphosphine (753 mg, 2.87 mmol), di-tert-butyl iminodicarboxylate (626 mg, 2.87 mmol), and diethyl azodicarboxylate (40% toluene solution) (1.25 g, 2.87 mmol) were added at room temperature and the resultant mixture was stirred for 1 hour and 30 minutes. After completion of the reaction, the reaction solution was concentrated under reduced pressure and 4 M hydrogen chloride/1,4-dioxane solution (7.5 mL) was added to the obtained residue, followed by stirring the resultant mixture for 1 day. After completion of the reaction, water and ethyl acetate were added to the reaction solution and the resultant mixture was washed with ethyl acetate. Thereafter, 1 M sodium hydroxide aqueous solution was added to the water phase and extraction from the resultant mixture with chloroform was performed. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product of the title compound (120 mg).

Workup

  1. additionwere added at room temperature
  2. customAfter completion of the reaction
  3. concentrationthe reaction solution was concentrated under reduced pressure and 4 M hydrogen chloride/1,4-dioxane solution (7.5 mL)
  4. additionwas added to the obtained residue
  5. customAfter completion of the reaction, water and ethyl acetate
  6. additionwere added to the reaction solution
  7. washthe resultant mixture was washed with ethyl acetate
  8. additionThereafter, 1 M sodium hydroxide aqueous solution was added to the water phase and extraction from the resultant mixture with chloroform
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-311d17f5ec0449b19882e267812b3380
Source dataset
uspto-grants-2016_08
Patent number
US09403798B2

Reaction notes

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