Phthalimide → 2-((1,3-Dioxoisoindolin-2-yl)methyl)-5-fluorobenzonitrile

HRID 348151Notes

Reaction equation

HRID 348151 reaction equation
Br[CH2:2][C:3]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:4]=1[C:5]#[N:6].[C:12]1(=[O:22])[NH:16][C:15](=[O:17])[C:14]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:13]12.C([O-])([O-])=O.[Cs+].[Cs+].C([O-])([O-])=O.[K+].[K+]>CN(C)C=O.O.CO.O>[O:17]=[C:15]1[C:14]2[C:13](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:12](=[O:22])[N:16]1[CH2:2][C:3]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:4]=1[C:5]#[N:6]

Participants

8

Reactant 4

HCID 6809PhthalimideHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 220157702-(Bromomethyl)-5-fluorobenzonitrile

Product 1

HCID 210697772-((1,3-Dioxoisoindolin-2-yl)methyl)-5-fluorobenzonitrileYield 99.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a stirred solution of intermediate 104, 2-(bromomethyl)-5-fluorobenzonitrile (29.72 g, 139 mmol) and phthalimide (32.69 g, 222 mmol) in dimethylformamide (300 mL) was added Cs2CO3 (67.87 g, 208 mmol). After stirring vigorously for 1 h, the reaction mixture was poured into water (1.2 L). The precipitated product was filtered, washed with water (600 mL) and methanol (150 mL) to give a white solid. The solid was taken up into 1 L of water/methanol (2:1) to which was added K2CO3 (12 g) and the mixture stirred at 40° C. After 30 min., the mixture was cooled and filtered. The filter cake was washed with water (500 mL), and dried under vacuum to afford the title compound (38.91 g, 94% yield) as a white powder. 1H NMR (500 MHz, CDCl3) δ: 7.89 (2H, dd, J=5.5, 3.1 HZ), 7.76 (5.5, 3.1 Hz), 7.41 (1H, dd, J=8.6, 5.2 Hz), 7.38 (1H, dd, J=7.9, 2.8 Hz), 7.24 (1H, td, J 8.2, 2.8 Hz), 5.06 (2H, s). LCMS (M+H) calcd for C16H10FN2O2: 281.07; found: 281.15.

Workup

  1. filtrationThe precipitated product was filtered
  2. washwashed with water (600 mL) and methanol (150 mL)
  3. customto give a white solid
  4. stirringthe mixture stirred at 40° C
  5. waitAfter 30 min.
  6. temperaturethe mixture was cooled
  7. filtrationfiltered
  8. washThe filter cake was washed with water (500 mL)
  9. customdried under vacuum

Sources & evidence

ORD record
ord-9708564e05274ec59fee91a56e5bc484
Source dataset
uspto-grants-2007_02
Patent number
US07176196B2

Reaction notes

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