Triphenylphosphine → 2-{[Bis(benzyloxy)phosphoryl]oxy}ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047153Notes

Reaction equation

HRID 1047153 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]([O:16][CH2:17][CH2:18][OH:19])=[O:15])[C:5]2=[O:20].[P:21](O)([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=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][CH2:17][CH2:18][O:19][P:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:22])=[O:15])[C:5]2=[O:20]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 74189Dibenzyl phosphateHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 687468242-Hydroxyethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Product 1

HCID 687488382-{[Bis(benzyloxy)phosphoryl]oxy}ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateYield 43.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Hydroxyethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 23, 100 mg, 0.29 mol), dibenzyl hydrogen phosphate (65 mg, 0.23 mmol) and triphenylphosphine (192 mg, 0.733 mmol) were dissolved in tetrahydrofuran (15 mL). Diisopropyl azodicarboxylate [DIAD] (106 mg, 0.52 mmol) was added drop wise and the mixture was stirred for 4 h at room temperature. The reaction 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 sulphate, filtered and concentrated under reduced pressure to give a crude compound. The crude compound was purified by flash column chromatography over silica gel (10-50% ethyl acetate/petroleum ether) to afford 60 mg (40%) of 2-{[bis(benzyloxy)phosphoryl]oxy}ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate.

Workup

  1. concentrationThe reaction 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 sulphate
  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 (10-50% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-e1c5d17aac4847388d9c5a1e4231ebb8
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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