Toluene → 5-hydroxymethyl-4-{[(6-chloropyridin-3-yl)methyl]amino}furan-2(5H)-one

HRID 552916Notes

Reaction equation

HRID 552916 reaction equation
O[C:2]1[CH:6]([CH2:7][OH:8])[O:5][C:4](=[O:9])[CH:3]=1.[NH2:10][CH2:11][C:12]1[CH:13]=[N:14][C:15]([Cl:18])=[CH:16][CH:17]=1.C1(C)C=CC=CC=1.CN(C)C=O>C1(C)C=CC(S(O)(=O)=O)=CC=1.O.C(O)(=O)C>[OH:8][CH2:7][CH:6]1[O:5][C:4](=[O:9])[CH:3]=[C:2]1[NH:10][CH2:11][C:12]1[CH:13]=[N:14][C:15]([Cl:18])=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 6228DimethylformamideHCID 70209275-(Aminomethyl)-2-chloropyridineHCID 671646764-hydroxy-5-hydroxymethylfuran-2(5H)-one

Product 1

HCID 866324475-hydroxymethyl-4-{[(6-chloropyridin-3-yl)methyl]amino}furan-2(5H)-oneYield 22.3%

Reagents, catalysts & solvents 3

HCID 6101p-Toluenesulfonic acidCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

905.0 mg (6.95 mmol) of 4-hydroxy-5-hydroxymethylfuran-2(5H)-one (VII-1a) and 991.8 mg (6.95 mmol) of 3-aminomethyl-6-chloropyridine are stirred in the mixture of 100.5 ml of toluene and 10 ml of N,N-dimethylformamide (DMF), and 10 mg of para-toluenesulphonic acid and 0.5 ml of acetic acid are added. With stirring, the entire reaction mixture is then heated at reflux on a water separator for about 18 hours. Concentration under reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm; mobile phase: cyclohexane/acetone=1:1) gives 394.2 mg (22.2% of theory) of 5-hydroxymethyl-4-{[(6-chloropyridin-3-yl)methyl]amino}furan-2(5H)-one.

Workup

  1. additionare added
  2. customthe entire reaction mixture
  3. temperatureis then heated
  4. concentrationConcentration
  5. customunder reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm; mobile phase: cyclohexane/acetone=1:1)

Sources & evidence

ORD record
ord-5e307ffabb1347589046470e52f20a7c
Source dataset
uspto-grants-2011_05
Patent number
US07951951B2

Reaction notes

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