Triphenylphosphine → 3-Hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047152Notes

Reaction equation

HRID 1047152 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]([C:14]([OH:16])=[O:15])[C:5]2=[O:17].[C:18]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:23]=CC=C[CH:19]=1.N(C(OCC)=O)=NC(OCC)=[O:40]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]([C:14]([O:16][CH2:19][CH2:18][CH2:23][OH:40])=[O:15])[C:5]2=[O:17]

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 215291746-Bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid3×

Product 1

HCID 687508073-Hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-Bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (2.0 g, 6.73 mM), propane-1,3-diol (Intermediate 22, 2.047 g, 26.93 mmol) and triphenylphosphine (7.058 g, 26.93 mmol) were dissolved in tetrahydrofuran (80 mL). Diethyl azodicarboxylate (DEAD) (3.51 g, 20.02 mmol) was added and the mixture was stirred for 16 h at room temperature. The solvent was evaporated under reduced pressure and water (100 mL) was added to the residue. The aqueous mixture was extracted with ethyl acetate (2×100 mL) and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a crude compound. The crude compound was purified by flash column chromatography over silica gel (100-200 mesh) and the product was eluted with a gradient of 50% ethyl acetate/petroleum ether to 100% ethyl acetate to afford 1.8 g (80%) of 3-hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate.

Workup

  1. customThe solvent was evaporated under reduced pressure and water (100 mL)
  2. additionwas added to the residue
  3. extractionThe aqueous mixture was extracted with ethyl acetate (2×100 mL)
  4. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a crude compound
  8. customThe crude compound was purified by flash column chromatography over silica gel (100-200 mesh)
  9. washthe product was eluted with a gradient of 50% ethyl acetate/petroleum ether to 100% ethyl acetate

Sources & evidence

ORD record
ord-29994902ecf94c249a087b57160b34f2
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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