1,8-Diazabicyclo(5.4.0)undec-7-ene → 1,6-Naphthyridine-8-methanol

HRID 1861680Notes

Reaction equation

HRID 1861680 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[N:5][CH:6]=[C:7]2[C:12]=1[N:11]=[CH:10][CH:9]=[CH:8]2.C1C=CC(P([N:27]=[N+:28]=[N-:29])(C2C=CC=CC=2)=O)=CC=1.[CH2:30]1[CH2:40][CH2:39][N:38]2[C:33](=[N:34][CH2:35][CH2:36][CH2:37]2)[CH2:32][CH2:31]1>CCOC(C)=O>[OH:1][CH2:2][C:3]1[CH:4]=[N:5][CH:6]=[C:7]2[C:12]=1[N:11]=[CH:10][CH:9]=[CH:8]2.[N:27]([CH2:30][C:40]1[CH:39]=[N:38][CH:37]=[C:36]2[C:35]=1[N:34]=[CH:33][CH:32]=[CH:31]2)=[N+:28]=[N-:29]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene3×HCID 199401P,P-Diphenylphosphinic azide3×HCID 120187001,6-Naphthyridine-8-methanol

Product 2

HCID 120187001,6-Naphthyridine-8-methanolHCID 12018701HCID 12018701, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.93 g (5.8 mmol) 8-hydroxymethyl-1,6-napthyridine in 20 mL TBF was added 1.5 mL (7 mmol) DPPA and 1.2 mL (6.7 mmol) DBU. The reaction mixture was allowed to stir at room temperature 18 hours, then another 0.3 mL DPPA and 0.25 mL DBU were added and the reaction mixture heated to 50° C. for 8 hours then cooled to room temperature then another 0.3 mL DPPA and 0.25 mL DBU were added and the reaction mixture was allowed to stir 18 more hours at room temperature. The resulting solution was then diluted with 200 L EtOAc, washed with saturated NaHCO3 solution, and brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (40×120 mm silica gel, linear gradient 2-15% MeOH:CH2Cl2) yielded 8-hydroxymethyl-1,6-napthyridine and 8-azidomethyl-1,6-napthyridine. 1H NMR (CDCl3, 400 MHz) δ 9.30 (s, 1H); 9.16 (dd, 1H, J=4.3 and 1.8 Hz); 8.78 (s, 1H); 8.35 (dd, 1H, J=8.3 and 1.74 Hz); 7.61 (dd, 1H, J=8.3 and 4.3 Hz); 5.00 (s, 2H).

Workup

  1. temperaturethe reaction mixture heated to 50° C. for 8 hours
  2. temperaturethen cooled to room temperature
  3. stirringto stir 18 more hours at room temperature
  4. washwashed with saturated NaHCO3 solution, and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography (40×120 mm silica gel, linear gradient 2-15% MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-a92165798b7f42ebbaacd136be1add68
Source dataset
uspto-grants-2003_03
Patent number
US06534510B2

Reaction notes

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