Monobasic potassium phosphate → 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HRID 245781Notes

Reaction equation

HRID 245781 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1.Cl([O-])=[O:22].[Na+].P([O-])(O)(O)=O.[K+]>O1CCOCC1.O>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([C:11]([OH:22])=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 584385252-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidYield 114%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

In a flask 2-bromo-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (3.11 g, 8.74 mmol) was dissolved in dioxane (120 mL) and H2O (30 mL) and the mixture cooled at 0° C. Sufamic acid (5.09 g, 52.4 mmol) was added, followed by a solution of sodium chlorite (1.28 g, 11.4 mmol) and potassium dihydrogen phosphate (14.3 g, 104.9 mmol) in H2O (75 mL) via an addition funnel over 15 min. The mixture was allowed to warm to room temperature over 2 h. The resulting yellow solid was filtered off, washed with H2O and hexane and dried. The filtrate was then extracted with EtOAc, and the combined organics washed with brine, dried over MgSO4 and concentrated to give additional product. In total 3.71 g of 2-bromo-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid was obtained as a yellow solid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 8.52 (s, 1H), 8.42 (s, 1H), 5.73 (s, 2H), 3.56-3.65 (m, 2H), 0.90-1.02 (m, 2H), 0.00 (s, 9H).

Workup

  1. filtrationThe resulting yellow solid was filtered off
  2. washwashed with H2O and hexane
  3. customdried
  4. extractionThe filtrate was then extracted with EtOAc
  5. washthe combined organics washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customto give additional product

Sources & evidence

ORD record
ord-30da20e74f76451fa8f461579715a92e
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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