2,5-dibromopyrazine → 3-(5-Bromo-2-pyrazinyl)-3-oxetanol

HRID 626983Notes

Reaction equation

HRID 626983 reaction equation
Br[C:2]1[CH:7]=[N:6][C:5]([Br:8])=[CH:4][N:3]=1.C([Li])CCC.[O:14]1[CH2:17][C:16](=[O:18])[CH2:15]1>C1(C)C=CC=CC=1>[Br:8][C:5]1[N:6]=[CH:7][C:2]([C:16]2([OH:18])[CH2:17][O:14][CH2:15]2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 114704212,5-dibromopyrazineHCID 150242543-OxetanoneHCID 178418339Butyllithium

Product 1

HCID 899233983-(5-Bromo-2-pyrazinyl)-3-oxetanolYield 48.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

2,5-Dibromopyrazine (1 g, 4.2 mmol) was dissolved in toluene (20 mL) under nitrogen and cooled to −78° C. n-Butyllithium (2.5M solution in hexanes, 1.77 mL) was added slowly with stirring and allowed to stir for a further 10 minutes upon complete addition. Oxetan-3-one (270 μL, 4.62 mmol) was added, and the reaction mixture was stirred at −78° C. for 30 minutes. The reaction mixture was allowed to warm to room temperature and the solvent was removed in vacuo. The residue was taken up in DCM (50 mL) and washed with saturated aqueous sodium bicarbonate solution (40 mL). The aqueous layer was re-extracted with DCM (50 mL). The organic extracts were combined, dried over sodium sulfate and concentrated in vacuo. The crude brown oil was purified by chromatography on silica (Biotage, 25 g cartridge), eluting with 0 to 100% ethyl acetate in heptanes, to afford the title compound (470 mg, 45%) as a yellow solid. Method B HPLC-MS: MH+ m/z 231, RT 1.13 minutes.

Workup

  1. additionwas added slowly
  2. stirringto stir for a further 10 minutes upon complete addition
  3. stirringthe reaction mixture was stirred at −78° C. for 30 minutes
  4. customthe solvent was removed in vacuo
  5. washwashed with saturated aqueous sodium bicarbonate solution (40 mL)
  6. extractionThe aqueous layer was re-extracted with DCM (50 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe crude brown oil was purified by chromatography on silica (Biotage, 25 g cartridge)
  10. washeluting with 0 to 100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-f6f4c73faebc417aa4bdc3ea2706134b
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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