Sodium Cyanide → 3-Chloro-2-cyanomethylbenzoic acid methyl ester

HRID 915356Notes

Reaction equation

HRID 915356 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:5]=1[CH2:11]Br.[C-:14]#[N:15].[Na+]>CN(C=O)C.CCOCC.O>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:5]=1[CH2:11][C:14]#[N:15]

Participants

6

Reactant 2

HCID 8929Sodium CyanideHCID 110327262-Bromomethyl-3-chloro-benzoic acid methyl ester

Product 1

HCID 668839793-Chloro-2-cyanomethylbenzoic acid methyl esterYield 65%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of crude 2-bromomethyl-3-chlorobenzoic acid methyl ester (30.4 mmol) in DMF (60 mL), was added finely powdered sodium cyanide (2.22 g, 45 mmol). The reaction mixture turned brown rapidly, and became warm. The dark suspension was then immersed in an oil bath held at 55° C. The reaction mixture was allowed to stir at 55° C. for 1.5 hours, at which time heating was discontinued, and the reaction was allowed to cool to ambient temperature. After stirring at ambient temperature for 16 hours, the reaction was diluted with ether (300 mL) and water (200 mL). The layers were separated, the aqueous was extracted with ether (3×75 mL), and the combined organic extracts were washed with water (3×50 mL). The organic layer was then washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a yellow oil. The crude oil was purified by flash chromatography eluting with a gradient from 0% to 16% ethyl acetate/hexane to afford 3-chloro-2-cyanomethylbenzoic acid methyl ester (3.9 g, 65% yield over two steps) as a white solid: 1H-NMR (400 MHz, CDCl3): δ 7.96 (1H, dd, J=8.1 Hz, 1.3 Hz), 7.65 (1H, dd, J=8.1, 1.3), 7.4 (1H, t, J=7.9Hz), 4.35 (2H, s), 3.97 (3H, s) ppm.

Workup

  1. temperaturebecame warm
  2. customThe dark suspension was then immersed in an oil bath
  3. customheld at 55° C
  4. temperatureheating
  5. temperatureto cool to ambient temperature
  6. stirringAfter stirring at ambient temperature for 16 hours
  7. customThe layers were separated
  8. extractionthe aqueous was extracted with ether (3×75 mL)
  9. washthe combined organic extracts were washed with water (3×50 mL)
  10. washThe organic layer was then washed with brine (100 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto afford a yellow oil
  15. customThe crude oil was purified by flash chromatography
  16. washeluting with a gradient from 0% to 16% ethyl acetate/hexane

Sources & evidence

ORD record
ord-b0172cedec4c4ee5946b2440c35b1599
Source dataset
uspto-grants-2007_09
Patent number
US07265131B2

Reaction notes

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