Hydrochloric Acid → 1,6-Naphthyridine

HRID 428544Notes

Reaction equation

HRID 428544 reaction equation
OS(O)(=O)=O.O[CH2:7][CH:8]([CH2:10]O)O.[Na+].[N+](C1C=C(S([O-])(=O)=O)C=CC=1)([O-])=O.[NH2:26][C:27]1[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=1.[OH-].[Na+].Cl>CCOC(C)=O.O>[N:26]1[C:27]2[C:28](=[CH:29][N:30]=[CH:31][CH:32]=2)[CH:10]=[CH:8][CH:7]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 753GlycerolHCID 1118Sulfuric AcidHCID 17274-AminopyridineHCID 14798Sodium HydroxideHCID 31389Sodium 3-nitrobenzenesulfonate

Product 1

HCID 674881,6-Naphthyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

A sulfuric acid solution was prepared by adding H2SO4 (100 mL) to H2O (57 mL) cooled in an ice bath. To this solution was added glycerol (33 mL, 457 mmol), m-nitrobenzene sulfonic acid sodium salt (48 g, 212 mmol) and 4-amino-pyridine (10 g, 106 mmol). The reaction mixture was heated at 135° C. for 4 hours. The cooled reaction mixture was basicified with 2.5 N NaOH (500 mL) with cooling in an ice bath, and extracted into CH2Cl2 (3×200 mL). The organic fractions were combined, dried over Na2SO4 and concentrated. The resulting oil was purified by column chromatography (5% MeOH/CH2Cl2) affording 5.04 g (36%) as a dark orange oil. An analytical sample was prepared as the HCl salt from EtOAc yielding an orange low melting solid. MS EI m/z 130 M+.

Workup

  1. temperaturecooled in an ice bath
  2. customThe cooled reaction mixture
  3. temperaturewith cooling in an ice bath
  4. extractionextracted into CH2Cl2 (3×200 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe resulting oil was purified by column chromatography (5% MeOH/CH2Cl2)
  8. customaffording 5.04 g (36%) as a dark orange oil

Sources & evidence

ORD record
ord-5a0791d741b24afbb157a1c86a979d38
Source dataset
uspto-grants-2001_11
Patent number
US06313126B1

Reaction notes

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