Cyclopentanone → 4-(1-Cyanocyclopentylamino)-2-fluorobenzonitrile

HRID 245027Notes

Reaction equation

HRID 245027 reaction equation
[C-:1]#[N:2].[Na+].[NH2:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([F:13])[CH:6]=1.[C:14]1(=O)[CH2:18][CH2:17][CH2:16][CH2:15]1>C(O)(=O)C>[C:1]([C:14]1([NH:4][C:5]2[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([F:13])[CH:6]=2)[CH2:18][CH2:17][CH2:16][CH2:15]1)#[N:2]

Participants

5

Reactant 3

HCID 8452CyclopentanoneHCID 8929Sodium CyanideHCID 27834134-Amino-2-fluorobenzonitrile

Product 1

HCID 671319804-(1-Cyanocyclopentylamino)-2-fluorobenzonitrileYield 90.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Sodium cyanide (0.74 g, 15 mmol) was added to a mixture of 4-amino-2-fluorobenzonitrile (1.36 g, 10 mmol) and cyclopentanone (1.26 g, 15 mmol) in 90% acetic acid (10 ml). The reaction mixture was stirred at room temperature for 3 hours and then the medium was hearted to 80° C. and stirred for an additional 5 hours. The medium was washed with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, concentrated and chromatographed (dichloromethane:acetone, 97:3) to yield 4-(1-cyanocyclopentylamino)-2-fluorobenzonitrile (54b) (2.07 g, 9.03 mmol, 90%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 1.69-1.91 (m, 4H), 2.13-2.18 (m, 2H), 2.37-2.42 (m, 2H), 5.08 (bs, 1H), 6.54-6.62 (m, 2H), 7.39 (t, J=7.3 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 23.7, 39.8, 56.8, 89.6 (d, J=15.8 Hz), 101.2 (d, J=23.8 Hz), 110.9, 115.2, 120.8, 134.1 (d, J=2.4 Hz), 150.3 (d, J=11.2 Hz), 164.5 (d, J=254.1 Hz).

Workup

  1. customwas hearted to 80° C.
  2. stirringstirred for an additional 5 hours
  3. washThe medium was washed with water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. concentrationconcentrated
  7. customchromatographed (dichloromethane:acetone, 97:3)

Sources & evidence

ORD record
ord-5ec6be2bf23044dea7b6ba0f531672cb
Source dataset
uspto-grants-2014_02
Patent number
US08658681B2

Reaction notes

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