Hydrochloric Acid → Ethyl 3-chloro-2-cyanobenzoate

HRID 1889052Notes

Reaction equation

HRID 1889052 reaction equation
Cl.N[C:3]1[C:13]([Cl:14])=[CH:12][CH:11]=[CH:10][C:4]=1[C:5]([O:7][CH2:8][CH3:9])=[O:6].N([O-])=O.[Na+].C([O-])([O-])=O.[Na+].[Na+].[C-:25]#[N:26].[K+]>O.C1(C)C=CC=CC=1.S([O-])([O-])(=O)=O.[Cu+2].CCOC(C)=O>[Cl:14][C:13]1[C:3]([C:25]#[N:26])=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 9032Potassium CyanideHCID 10340Sodium CarbonateHCID 12143958Ethyl 2-amino-3-chlorobenzoateHCID 23668193Sodium Nitrite

Product 1

HCID 14696600Ethyl 3-chloro-2-cyanobenzoate

Reagents, catalysts & solvents 4

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Hydrochloric acid (4.57 mL, 150 mmol) was added to a suspension of the ethyl 2-amino-3-chlorobenzoate (1.5 g, 7.51 mmol) in water (40 mL) and the mixture was cooled to 0° C. [note: compound did not go into solution] To this cooled mixture was added sodium nitrite (0.518 g, 7.51 mmol) portionwise keeping the temperature below 5° C. After addition the reaction was stirred for 40 mins. A small amount of toluene (3 ml) was added to aid dissolution. The mixture was then basified to pH˜6 by the addition of Na2CO3. In a separate flask potassium cyanide (2.202 g, 33.8 mmol) was added portionwise to a biphasic solution of copper(II) sulfate (1.439 g, 9.02 mmol) in water (15 mL) and toluene (15 mL) at 0° C. [note: exothermic reaction] After addition the now brown mixture was heated to 60° C. To this was added the diazonium salt dropwise via a dropping funnel (mixture kept at 0° C. during addition). After addition the reaction was stirred at 70° C. for 1 hr. The reaction was cooled and EtOAc was added. The organic layer was collected, dried (Na2SO4) and the solvent evaporated to afford a crude dark brown oil. LCMS: 2 major peaks+1 minor peak present. (One major peak corresponds to the SM—no mass ion observed). The crude material was purified by chromatography, SP4, 100 g SNAP, 0 to 100% EtOAc/i-Hexane (fasted eluting first). The desired product was identified in 398 mg.

Workup

  1. customthe temperature below 5° C
  2. additionAfter addition the reaction
  3. custom[note: exothermic reaction]
  4. additionAfter addition the now brown mixture
  5. temperaturewas heated to 60° C
  6. addition(mixture kept at 0° C. during addition)
  7. additionAfter addition the reaction
  8. stirringwas stirred at 70° C. for 1 hr
  9. temperatureThe reaction was cooled
  10. customThe organic layer was collected
  11. dry with materialdried (Na2SO4)
  12. customthe solvent evaporated
  13. customto afford a crude dark brown oil
  14. customThe crude material was purified by chromatography, SP4, 100 g SNAP, 0 to 100% EtOAc/i-Hexane (fasted eluting first)

Sources & evidence

ORD record
ord-f5d052f060e343559b366f32281a03a5
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

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