Sodium hydride → (E)-3-[5-(4-Fluorophenyl)-1,2-dihydro-7-isopropyl-2-oxo1, 8-naphthyridin-6-yl]-prop-2-enal

HRID 1087048Notes

Reaction equation

HRID 1087048 reaction equation
C1(NC=CP(=O)(OCC)[O:11][CH2:12][CH3:13])CCCCC1.[H-].[Na+].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:36]([CH:37]=O)=[C:35]([CH:39]([CH3:41])[CH3:40])[N:34]=[C:33]3[C:28]=2[CH:29]=[CH:30][C:31](=[O:42])[NH:32]3)=[CH:23][CH:22]=1.O.O.C(O)(=O)C(O)=O>O1CCCC1.O.C1(C)C=CC=CC=1>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[C:36](/[CH:37]=[CH:13]/[CH:12]=[O:11])=[C:35]([CH:39]([CH3:40])[CH3:41])[N:34]=[C:33]3[C:28]=2[CH:29]=[CH:30][C:31](=[O:42])[NH:32]3)=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 61373Oxalic acid dihydrateHCID 89268Diethyl [2-(cyclohexylamino)vinyl]phosphonateHCID 148505585-(4-Fluorophenyl)-6-formyl-1,2-dihydro-7-isopropyl-2-oxo-1,8-naphthyridine

Product 1

HCID 14850559(E)-3-[5-(4-Fluorophenyl)-1,2-dihydro-7-isopropyl-2-oxo1, 8-naphthyridin-6-yl]-prop-2-enal

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 13.1 g (50 mmol) of diethyl 2-(cyclohexylamino)-vinyl-phosphonate in 80 ml of tetrahydrofuran is added dropwise at 0° C. under argon to a suspension of 3.0 g (100 mmol) of 80% strength sodium hydride in 80 ml of anhydrous tetrahydrofuran and the mixture is stirred at this temperature for 30 min. A solution of 13.0 g (42 mmol) of the compound from Example 4 in 80 ml of tetrahydrofuran is then added dropwise at 0° C.-5° C. and the mixture is then heated under reflux for 1 h. 200 ml of water are added cautiously and the mixture is extracted three times with ethyl acetate. After concentrating the organic phases, the residue is heated under reflux for 2 h with a mixture of 500 ml of toluene, 500 ml of water and 27.5 g (218 mmol) of oxalic acid dihydrate. The toluene phase is concentrated and the residue is treated with ethyl acetate. 11.35 g (80% of theory) of colorless crystals of m.p. 261° C. are obtained.

Workup

  1. temperaturethe mixture is then heated
  2. temperatureunder reflux for 1 h
  3. extractionthe mixture is extracted three times with ethyl acetate
  4. concentrationAfter concentrating the organic phases
  5. temperaturethe residue is heated
  6. concentrationThe toluene phase is concentrated
  7. additionthe residue is treated with ethyl acetate
  8. custom11.35 g (80% of theory) of colorless crystals of m.p. 261° C. are obtained

Sources & evidence

ORD record
ord-d28aec44ba5846a2a9d14544a492910a
Source dataset
uspto-grants-1991_07
Patent number
US05034399

Reaction notes

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