Methyl 2-cyano-4-fluorobenzoate → 5-fluoro-2,3-dihydro-1H-isoindol-1-one

HRID 872162Notes

Reaction equation

HRID 872162 reaction equation
[C:1]([C:3]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:4]=1[C:5](OC)=[O:6])#[N:2]>C(O)C>[F:13][C:11]1[CH:12]=[C:3]2[C:4](=[CH:9][CH:10]=1)[C:5](=[O:6])[NH:2][CH2:1]2

Participants

3

Reactant 1

HCID 9989818Methyl 2-cyano-4-fluorobenzoate

Product 1

HCID 197880975-fluoro-2,3-dihydro-1H-isoindol-1-oneYield 76.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 250-mL Parr reactor bottle was purged with nitrogen and charged with Raney nickel (4.00 g) and a solution of 106a (2.00 g, 11.2 mmol) in ethanol (20 mL). The bottle was attached to a Parr hydrogenator, evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 16 h. After this time, the hydrogen was evacuated, and nitrogen was charged into the bottle. Celite 521 (5.00 g) was added, and the mixture was filtered through a pad of Celite 521. The filter cake was washed with ethanol (2×75 mL), and the combined filtrates were concentrated to dryness under reduced pressure to afford a 76% yield of 106b (1.29 g) as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.85 (dd, 1H, J=8.5, 5.5 Hz), 7.21-7.16 (m, 2H), 7.05 (br s, 1H), 4.56 (s, 2H).

Workup

  1. customA 250-mL Parr reactor bottle was purged with nitrogen
  2. additioncharged with Raney nickel (4.00 g)
  3. customevacuated
  4. additioncharged with hydrogen gas to a pressure of 50 psi
  5. customAfter this time, the hydrogen was evacuated
  6. additionnitrogen was charged into the bottle
  7. additionCelite 521 (5.00 g) was added
  8. filtrationthe mixture was filtered through a pad of Celite 521
  9. washThe filter cake was washed with ethanol (2×75 mL)
  10. concentrationthe combined filtrates were concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-076577aebd0c44ff994bdc18bdb03ff5
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

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