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

HRID 1047154Notes

Reaction equation

HRID 1047154 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][CH2:19][OH:20])=[O:15])[C:5]2=[O:21].[P:22](O)([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23].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][CH2:19][O:20][P:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:23])=[O:15])[C:5]2=[O:21]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 74189Dibenzyl phosphateHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 687508073-Hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Product 1

HCID 687490433-{[Bis(benzyloxy)phosphoryl]oxy}propyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 24, 100 mg, 0.28 mmol), dibenzyl hydrogen phosphate (124 mg, 0.44 mmol) and triphenylphosphine (367 mg, 1.4 mmol) was dissolved in tetrahydrofuran (15 mL). Diisopropyl azodicarboxylate [DIAD] (281 mg, 1.40 mmol) was added 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 (0-50% ethyl acetate/petroleum ether) to afford 80 mg (47%) of 3-{[bis(benzyloxy)phosphoryl]oxy}propyl 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 (0-50% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-7fcd4471117e4884895dcfc8fb20ce31
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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