Ethyl Acetate → 8-Allyl-7-chloro-2-methoxy-[1,5]naphthyridine

HRID 633834Notes

Reaction equation

HRID 633834 reaction equation
[CH2:1]([Sn](CCCC)(CCCC)CCCC)[CH:2]=[CH2:3].Br[C:18]1[C:19]([Cl:30])=[CH:20][N:21]=[C:22]2[C:27]=1[N:26]=[C:25]([O:28][CH3:29])[CH:24]=[CH:23]2.[Cl-].[Li+].C(OCC)(=O)C>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:3]([C:18]1[C:19]([Cl:30])=[CH:20][N:21]=[C:22]2[C:27]=1[N:26]=[C:25]([O:28][CH3:29])[CH:24]=[CH:23]2)[CH:2]=[CH2:1]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 90628AllyltributylstannaneHCID 433294Lithium ChlorideHCID 513582238-Bromo-7-chloro-2-methoxy-1,5-naphthyridine

Product 1

HCID 671828908-Allyl-7-chloro-2-methoxy-[1,5]naphthyridineYield 58.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

Allyltributylstannane (7.3 g, 21.9 mmol, 1.2 eq) is added at room temperature to a stirred solution of 8-bromo-7-chloro-2-methoxy-[1,5]naphthyridine (5.0 g, 18.3 mmol, 1.0 eq) in N,N-dimethylformamide (100 mL), followed by tetrakis(triphenylphosphine)palladium(0) (0.63 g, 0.55 mmol, 0.03 eq) and lithium chloride (2.9 g, 67.6 mmol, 3.7 eq). After 1 hour stirring at 105° C., the reaction mixture is cooled down to room temperature and filtered through decalite. The filtrate is concentrated to give a crude product that is extracted with ethyl acetate (3×100 mL) and a 10% ammonium hydroxide aqueous solution (100 mL). The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product that is purified column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 30:1, v/v) to afford 8-allyl-7-chloro-2-methoxy-[1,5]naphthyridine as a colorless oil (2.5 g, 58% yield).

Workup

  1. temperaturethe reaction mixture is cooled down to room temperature
  2. filtrationfiltered through decalite
  3. concentrationThe filtrate is concentrated
  4. customto give a crude product that
  5. extractionis extracted with ethyl acetate (3×100 mL)
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a crude product that
  11. customis purified column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-8416ef73e9bb4acc8868d958f504023b
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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