Tetrabutylammonium Fluoride → 4-Amino-2-chloro-5-ethynylbenzonitrile

HRID 475272Notes

Reaction equation

HRID 475272 reaction equation
[NH2:1][C:2]1[C:9]([C:10]#[C:11][Si](C)(C)C)=[CH:8][C:5]([C:6]#[N:7])=[C:4]([Cl:16])[CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[NH2:1][C:2]1[C:9]([C:10]#[CH:11])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([Cl:16])[CH:3]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86222791HCID 86222791, compound

Product 1

HCID 866947484-Amino-2-chloro-5-ethynylbenzonitrileYield 99.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 238 (1.0 g, 4 mmol) in THF (100 mL) was added tetrabutylammonium fluoride (2.0 g, 7.6 mmol). The mixture was heated at 75° C. overnight then concentrated and the residue partitioned between EtOAc (500 mL) and H2O (50 mL). The organic layer was separated, washed with brine, concentrated to dryness in vacuo. The crude was purified by CombiFlash chromatography eluting with an EtOAc/petroleum ether gradient (10% to 45% EtOAc) to afford 700 mg (48%) 4-amino-2-chloro-5-ethynylbenzonitrile (240) as yellow solid: MS (ESI) m/z=177.0 [M+1]+.

Workup

  1. concentrationthen concentrated
  2. customthe residue partitioned between EtOAc (500 mL) and H2O (50 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. concentrationconcentrated to dryness in vacuo
  6. customThe crude was purified by CombiFlash chromatography
  7. washeluting with an EtOAc/petroleum ether gradient (10% to 45% EtOAc)

Sources & evidence

ORD record
ord-bf8a0827f91842a2b2cfb7eed4598c5a
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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