Sodium Cyanide → 4-Cyano-2-ethoxybenzoic acid

HRID 2105830Notes

Reaction equation

HRID 2105830 reaction equation
N[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:11][CH2:12][CH3:13])[CH:3]=1.N([O-])=O.[Na+].C(=O)(O)[O-].[Na+].[Cu][C:24]#[N:25].[C-]#N.[Na+]>Cl.O.C1C=CC=CC=1.[Cu]Cl>[C:24]([C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:11][CH2:12][CH3:13])[CH:3]=1)#[N:25]

Participants

10

Reactant 5

HCID 8929Sodium CyanideHCID 516892Sodium BicarbonateHCID 101763852-Ethoxy-4-aminobenzoic acidHCID 23668193Sodium NitriteHCID 178418546HCID 178418546, compound

Product 1

HCID 226750384-Cyano-2-ethoxybenzoic acidYield 53%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 241BenzeneSolventHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×

Procedure

To a cooled solution of 4-amino-2-ethoxybenzoic acid (500 mg, 2.76 mmol) in 2 M hydrochloric acid (1.0 mL) was added a solution of sodium nitrite (192 mg, 2.8 mmol) in water (0.55 mL). The mixture was stirred for 15 min and neutralized by adding small amounts of solid sodium bicarbonate. This solution was then added to a freshly prepared solution of copper(I) cyanide at 0° C. (prepared from sodium cyanide and copper(I) chloride according to Org. Syn. Coll. Vol VI, p. 514) in water (7.5 mL) and benzene (2.5 mL). The reaction was allowed to warm up to room temperature and stirred for 2 h. The mixture was filtered through Celite and the filtrate extracted with ethyl acetate. The aqueous phase was acidified with 2 M hydrochloric acid and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated to give 4-cyano-2-ethoxybenzoic acid as a light brown solid (280 mg, 53%), which was used in the next step without further purification.

Workup

  1. stirringstirred for 2 h
  2. filtrationThe mixture was filtered through Celite
  3. extractionthe filtrate extracted with ethyl acetate
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4b2f12535ded496f8c0b4444cf740d4e
Source dataset
uspto-grants-2009_08
Patent number
US07579368B2

Reaction notes

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