Sodium Hydroxide → 8-Chloro-3-fluoro-1,5-naphthyridine

HRID 40362

Reaction equation

HRID 40362 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[CH:7]=[CH:8][NH:9]2)=[N:4][CH:3]=1.O=P(Cl)(Cl)[Cl:15].[OH-].[Na+].C(Cl)Cl.CO.[NH4+].[OH-]>C(Cl)Cl>[Cl:15][C:6]1[CH:7]=[CH:8][N:9]=[C:10]2[C:5]=1[N:4]=[CH:3][C:2]([F:1])=[CH:11]2

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 21896990Dichloromethane methanol ammonium hydroxideHCID 675043247-Fluoro-1,5-naphthyridin-4-ol

Product 1

HCID 576909378-Chloro-3-fluoro-1,5-naphthyridineYield 64.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

A pressure resistant vial was charged with 7-fluoro-1,5-naphthyridin-4(1H)-one (600 mg, 3.66 mmol) and POCl3 (6.8 mL, 73.1 mmol). Vessel sealed and stirred at 110° C. for 16 hrs. Reaction mixture was cooled to room temperature and poured onto ice while stirring vigorously. While keeping reaction mixture at 0° C., it was basified to pH˜8 with 6N NaOH. Product extracted with dichloromethane. Organic layer collected, dried over sodium sulfate and concentrated to afford desired material. This was passed through a silica plug in 1-5% (90:10:1 DCM/MeOH/NH4OH)/DCM to afford 8-chloro-3-fluoro-1,5-naphthyridine (430 mg, 64% yield) as a tan solid. MS [M+H]=182.9. Calc'd for C8H4ClFN2=182.58

Workup

  1. customVessel sealed
  2. customReaction mixture
  3. temperaturewas cooled to room temperature
  4. additionpoured onto ice
  5. stirringwhile stirring vigorously
  6. customreaction mixture at 0° C.
  7. extractionProduct extracted with dichloromethane
  8. customOrganic layer collected
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customto afford desired material

Sources & evidence

ORD record
ord-d2769fba50d040f2a1f4cc61c0e85a31
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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