Sodium Hydroxide → HCID 117696455, compound

HRID 2205285Notes

Reaction equation

HRID 2205285 reaction equation
[CH3:1][C:2]1[C:11]2[C:6](=[C:7](O)[N:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:16])=O.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[Cl:16][C:7]1[N:8]=[C:9]([CH3:12])[CH:10]=[C:11]2[C:6]=1[N:5]=[CH:4][CH:3]=[C:2]2[CH3:1]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychloride2×HCID 178421970HCID 178421970, compound

Product 1

HCID 117696455HCID 117696455, compoundYield 66.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
104 °C

Procedure

4,6-Dimethyl-[1,7]naphthyridin-8-ol (1.26 g, 7.23 mmol) and phosphorus oxychloride (6.7 mL, 72 mmol) in toluene (18 mL) are heated at 100° C. overnight. Phosphorus oxychloride (20 mL, 215 mmol) is added and the reaction mixture is heated at 104° C. for 1 d. The reaction mixture is cooled to RT and poured in a mixture of ice and water under stirring. After 30 min 20% NaOH is added until pH 6-7. The aqueous layer is extracted with DCM and the combined organic layers are washed with brine, dried and evaporated under reduce pressure to give a residue that is purified by flash chromatography (eluent 0-50% EtOAc/cyclohexane) to furnish 8-chloro-4,6-dimethyl-[1,7]naphthyridine (920 mg, 66%).

Workup

  1. temperatureThe reaction mixture is cooled to RT
  2. extractionThe aqueous layer is extracted with DCM
  3. washthe combined organic layers are washed with brine
  4. customdried
  5. customevaporated
  6. customto give a residue that
  7. customis purified by flash chromatography (eluent 0-50% EtOAc/cyclohexane)

Sources & evidence

ORD record
ord-93816607760e47dd85c5b668fe4e7b0d
Source dataset
uspto-grants-2016_06
Patent number
US09371282B2

Reaction notes

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