Ethanol → 2-(Dimethoxymethyl)-1,8-naphthyridine

HRID 1777852Notes

Reaction equation

HRID 1777852 reaction equation
[NH2:1][C:2]1[C:7]([CH:8]=O)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:10][O:11][CH:12]([O:16][CH3:17])[C:13](=O)[CH3:14].C(O)C.[OH-].[Na+]>O>[CH3:10][O:11][CH:12]([O:16][CH3:17])[C:13]1[CH:14]=[CH:8][C:7]2[C:2](=[N:3][CH:4]=[CH:5][CH:6]=2)[N:1]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 14798Sodium HydroxideHCID 80650Pyruvic aldehyde dimethyl acetalHCID 7376333-Pyridinecarboxaldehyde, 2-amino-

Product 1

HCID 177501752-(Dimethoxymethyl)-1,8-naphthyridine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
7.5 °C

Procedure

The procedure described in J. Org. Chem., 2004, 69 (6), pp 1959-1966 was used. Into a 20 l 4-necked round-bottom flask was placed 2-aminopyridine-3-carbaldehyde (1000 g, 8.19 mol), 1,1-dimethoxypropan-2-one (1257 g, 10.64 mol), ethanol (10 l), and water (2 l). This was followed by the addition of a solution of sodium hydroxide (409.8 g, 10.24 mol) in water (1000 ml) drop wise with stirring at 0-15° C. The solution was stirred for 3 h at 0-20° C. and then concentrated under vacuum. The resulting solution was extracted with 3×1200 ml of ethyl acetate and the organic layers were combined. The mixture was dried over sodium sulfate and concentrated under vacuum. The residue was washed with 3×300 ml of hexane and the solid was collected by filtration. This resulted in the title compound as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ 9.11 (dd, 1H), 8.53 (d, 1H), 8.50 (dd, 1H), 7.73 (d, 1H), 7.67 (dd, 1H), 5.44 (s, 1H), 3.41 (s, 6H).

Workup

  1. customInto a 20 l 4-necked round-bottom flask was placed
  2. stirringThe solution was stirred for 3 h at 0-20° C.
  3. concentrationconcentrated under vacuum
  4. extractionThe resulting solution was extracted with 3×1200 ml of ethyl acetate
  5. dry with materialThe mixture was dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. washThe residue was washed with 3×300 ml of hexane
  8. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-b870a49acdf746e69a6e6cbdb8a3c9ed
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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