3-Hydroxybenzaldehyde → HCID 22337095, compound

HRID 585508Notes

Reaction equation

HRID 585508 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].[O-]CC.[Na+].Cl[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21]([NH2:23])=[O:22])[CH:16]=1.OC1C=C(C=CC=1)C=O>CN(C=O)C>[OH:6][CH2:5][C:4]1[CH:3]=[C:2]([CH:9]=[CH:8][CH:7]=1)[O:1][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21]([NH2:23])=[O:22])[CH:16]=1

Participants

6

Reactant 4

HCID 1013-HydroxybenzaldehydeHCID 1023-Hydroxybenzyl alcoholHCID 3035434-Chloropyridine-2-carboxamideHCID 2723922Sodium ethoxide2×

Product 1

HCID 22337095HCID 22337095, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-Hydroxybenzyl alcohol (7.93 g, 63.8 mmol) is dissolved in 500 ml of DMF, sodium ethoxide (5.22 g, 76.6 mmol) is added, the mixture is stirred with exclusion of moisture for 15 min and 4-chloropyridine-2-carboxamide (D. Varlet et al. Heterocycles 2000, 53, 797-804) is then added. The mixture is stirred at 138° C. for 70 hours and again a solution of 4 g of 3-hydroxybenzaldehyde and 2.6 g of sodium ethoxide in 100 ml of DMF, which solution is stirred for 15 min, is added. The mixture is stirred at 138° C. for 12 h and then concentrated under reduced pressure. The residue is transferred into saturated KH2PO4 solution and extracted with ethyl acetate. The organic phase is washed with water. The combined aqueous phases are re-extracted with ethyl acetate. The combined dried organic phases are concentrated under reduced pressure and chromatographed on silica gel using a toluene/ethyl acetate gradient. This gives 5.04 g (32.3% of theory) of the target compound having a m.p. of 113° C. and an Rf (SiO2, ethyl acetate) of 0.49.

Workup

  1. stirringThe mixture is stirred at 138° C. for 70 hours
  2. additionis added
  3. stirringThe mixture is stirred at 138° C. for 12 h
  4. concentrationconcentrated under reduced pressure
  5. extractionextracted with ethyl acetate
  6. washThe organic phase is washed with water
  7. extractionThe combined aqueous phases are re-extracted with ethyl acetate
  8. concentrationare concentrated under reduced pressure
  9. customchromatographed on silica gel using a toluene/ethyl acetate gradient

Sources & evidence

ORD record
ord-6c52282c29c148888889ea78e2d07f78
Source dataset
uspto-grants-2005_08
Patent number
US06933295B2

Reaction notes

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