Ethyl Acetate → 2-{7-[(4-Fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol

HRID 513960Notes

Reaction equation

HRID 513960 reaction equation
FC1C=CC(C[O:7][C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13](C(OCC)=O)[CH:14]=[N:15]3)=[N:10][CH:9]=2)=CC=1.O[C:26]1C=C2C(C=C(C(OCC)=O)C=N2)=NC=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52]Cl)=[CH:50][CH:49]=1.CCO[C:59]([CH3:61])=[O:60]>CN(C=O)C.O>[F:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][O:7][C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([C:59]([OH:60])([CH3:61])[CH3:26])[CH:14]=[N:15]3)=[N:10][CH:9]=2)=[CH:50][CH:49]=1

Participants

8

Reactant 5

HCID 8857Ethyl AcetateHCID 96024-Fluorobenzyl chlorideHCID 10796Cesium carbonateHCID 90418013Ethyl 7-((4-fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylateHCID 136227102Ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate2×

Product 1

HCID 863016572-{7-[(4-Fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-olYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Ethyl 7-((4-fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylate. To a solution of ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate (Intermediate 4, 3.0 g, 13.75 mmol) in DMF (70 mL) was added Cs2CO3 (8.96 g, 0.03 mol), followed by 4-fluorobenzyl chloride (2.42 mL, 0.02 mol). The reaction was stirred at ambient temperature for 72 h. The crude reaction mixture was poured into EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic fractions were washed with brine and concentrated under reduced pressure onto silica. Purification (FCC, SiO2, 0-60%, EtOAc/hexanes) afforded the title compound as a white solid (3.0 g, 67%) 1H NMR (400 MHz, CDCl3) δ 9.45 (d, J=1.6 Hz, 1H), 8.97 (s, 1H), 8.85 (d, J=2.3 Hz, 1H), 7.72 (d, J=2.0 Hz, 1H), 7.48 (dd, J=5.5, 7.8 Hz, 2H), 7.12 (t, J=8.6 Hz, 2H), 5.22 (s, 2H), 4.48 (q, J=7.3 Hz, 2H), 1.46 (t, J=7.0 Hz, 3H). [M+H]=327.2

Workup

  1. customThe crude reaction mixture
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic fractions were washed with brine
  4. concentrationconcentrated under reduced pressure onto silica
  5. customPurification (FCC, SiO2, 0-60%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-0f9b0438488c4c24827b9953cac86f6a
Source dataset
uspto-grants-2015_08
Patent number
US09102674B2

Reaction notes

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