Sodium Cyanide → tert-Butyl-4-(cyanomethyl)-3-chlorobenzoate

HRID 1243278Notes

Reaction equation

HRID 1243278 reaction equation
[C-]#N.[Na+].[Cl:4][C:5]1[CH:10]=[C:9]([C:11]([OH:13])=[O:12])[CH:8]=[CH:7][C:6]=1[CH2:14][C:15]#[N:16].NC(=N)O>CN(C=O)C.O.C(OCC)(=O)C.C(Cl)Cl>[C:6]([O:12][C:11](=[O:13])[C:9]1[CH:8]=[CH:7][C:6]([CH2:14][C:15]#[N:16])=[C:5]([Cl:4])[CH:10]=1)([CH3:14])([CH3:7])[CH3:5]

Participants

8

Reactant 3

HCID 8929Sodium CyanideHCID 219250183-Chloro-4-(cyanomethyl)benzoic acidHCID 178513210HCID 178513210, compound

Product 1

HCID 21925016tert-Butyl-4-(cyanomethyl)-3-chlorobenzoateYield 95.3%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The foregoing compound was dissolved in DMF (3 mL) and cooled to 0° C. NaCN (2 equ) dissolved in 1 mL of water and 2 mL of DMF were added to the solution and the reaction mixture was stirred for 0.5 h. After diluting the mixture with ethyl acetate it was washed with aqueous ammonium sulfate and brine, dried (Na2SO4), filtered and evaporated to give a yellow solid which was directly used in the esterification step. 2-(2-Chloro-4-carboxyphenyl)-acetonitrile (0.391 g, 2 mmol) was treated with 2 equiv of isourea 4 in 35 mL of DCM at reflux over night. After evaporation of DCM, the crude was diluted in EtOAc (50 mL) and filtered. The filtrate was concentrated and purified by flash chromatography in silica gel eluting with 1% EtOAc in petroleum ether to give tert-Butyl-4-(cyanomethyl)-3-chlorobenzoate (0.24 g, 47% yield). 1H NMR (CDCl3, 400 MHz) δ 8.03 (d, J=1.6 Hz, 1 H), 7.93 (dd, J=8.02 Hz, J=1.62 Hz, 1 H), 7.60 (d, J=8.02 Hz, 1 H), 3.89 (s, 2 H), 1.61 (s, 9 H).

Workup

  1. washwas washed with aqueous ammonium sulfate and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. customto give a yellow solid which
  6. temperatureat reflux over night
  7. customAfter evaporation of DCM
  8. additionthe crude was diluted in EtOAc (50 mL)
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. custompurified by flash chromatography in silica gel eluting with 1% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-e1588f7b190243b2a3a9dc3d5d35fa29
Source dataset
uspto-grants-2006_10
Patent number
US07119073B2

Reaction notes

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