Ethylene Glycol → 2-Hydroxyethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047151Notes

Reaction equation

HRID 1047151 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].[CH2:18](O)[CH2:19][OH:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>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][CH2:18][CH2:19][OH:20])=[O:15])[C:5]2=[O:17]

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 215291746-Bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid2×

Product 1

HCID 687468242-Hydroxyethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-Bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (Intermediate 22, 1.7 g, 5.72 mmol), ethane-1,2-diol (1.91 g, 34.34 mmol) and triphenylphosphine (9.0 g, 34.34 mmol) were dissolved in tetrahydrofuran (100 mL). Diethyl azodicarboxylate (DEAD) (4.97 g, 28.61 mol) was added drop wise and the mixture was stirred for 16 h at room temperature. The mixture was concentrated under reduced pressure, and water (100 mL) was added. 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) using eluent gradient of ethyl acetate/petroleum ether: 1:1 to 100:0 to afford 1.6 g (82%) of 2-hydroxyethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure, and water (100 mL)
  2. additionwas added
  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)

Sources & evidence

ORD record
ord-bb011c78e9514f88bf1fdaa2d88c75c4
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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