Ethyl 4-hydroxy-3-iodobenzoate → Ethyl 3-cyano-4-hydroxybenzoate

HRID 746796Notes

Reaction equation

HRID 746796 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7](I)[CH:6]=1)[CH3:2].[C:14]([Cu])#[N:15]>CS(C)=O>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([C:14]#[N:15])[CH:6]=1)[CH3:2]

Participants

4

Reactant 2

HCID 11220038Ethyl 4-hydroxy-3-iodobenzoateHCID 178418546HCID 178418546, compound

Product 1

HCID 21322395Ethyl 3-cyano-4-hydroxybenzoate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
105 °C

Procedure

Charge a 10 L double jacket reactor, equipped with a mechanical stirrer, a reflux condenser and set under N2 with 4-hydroxy-3-iodo-benzoic acid ethyl ester (1312 g, 4.49 mol), dimethylsulfoxide (3277 mL) and CuCN (442.3 g). Heat the mixture to 105° C. and hold at this temperature for 2.5 h. Cool the brown solution down to 20° C. Add water at 48° C. water (6.5 L) Filter the mixture at 20° C., then wash the cake with water (2 L). Suspend the cake in EtOAc (5 L) and stir during 1 h at 20° C. Filter the suspension on Hyflo Super Cel® (250 g) and rinse with EtOAc (3 L). Decant the filtrates, then evaporate the organic layer to dryness. Take the residue up in n-heptane (10 L). Distill off 2 L of n-heptane, then add CH2Cl2 (400 mL). Cool the mixture cooled to 27° C., filter and rinse the cake with n-heptane (2 L). Dry 48 h at 55° C. under pressure to give 4-hydroxy-3-cyano-benzoic acid ethyl ester. (777.7 g, 4.067 mol). 1H NMR (250 MHz, DMSOd): 1.32 (t, j=7.1 Hz, 3H), 4.3 (q, j=7.1 Hz, 2H), 7.13(d, j=8.8 Hz, 1H), 8.07(dxd, j=8.8 Hz, 2.2 Hz, 1H), 8.16 (d, j=2.2 Hz), 12.11(s (broad), 1H).

Workup

  1. additionCharge a 10 L double jacket reactor
  2. customequipped with a mechanical stirrer, a reflux condenser
  3. temperatureCool the brown solution down to 20° C
  4. filtrationAdd water at 48° C. water (6.5 L) Filter the mixture at 20° C.
  5. washwash the cake with water (2 L)
  6. filtrationFilter the suspension on Hyflo Super Cel® (250 g)
  7. washrinse with EtOAc (3 L)
  8. customDecant the filtrates
  9. customevaporate the organic layer to dryness
  10. distillationDistill off 2 L of n-heptane
  11. temperatureCool the mixture
  12. temperaturecooled to 27° C.
  13. filtrationfilter
  14. washrinse the cake with n-heptane (2 L)
  15. customDry 48 h at 55° C. under pressure

Sources & evidence

ORD record
ord-2c6361616dbe4301a9006cddf8a70f2b
Source dataset
uspto-grants-2008_07
Patent number
US07393868B2

Reaction notes

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