Isopropanol → 5-isopropoxypyrazine-2-carboxylic acid

HRID 1526599Notes

Reaction equation

HRID 1526599 reaction equation
[CH3:1][C:2](C)([O-:4])[CH3:3].[Na+].CC(O)C.Cl[C:12]1[N:13]=[CH:14][C:15]([C:18]([O:20]C)=[O:19])=[N:16][CH:17]=1>C1COCC1>[CH:2]([O:4][C:12]1[N:13]=[CH:14][C:15]([C:18]([OH:20])=[O:19])=[N:16][CH:17]=1)([CH3:3])[CH3:1]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 642663795-isopropoxypyrazine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a rt solution of sodium t-butoxide (1.41 g, 14.67 mmol) in THF (20 mL) was added 2-propanol (1.250 mL, 16.33 mmol) dropwise. After 10 min a solution of methyl 5-chloro-2-pyrazinecarboxylate (1.70 g, 9.85 mmol, Ark Pharm) in THF (10 mL) was added dropwise. After 1.5 h, the reaction was quenched with saturated aq NH4Cl and extracted with EtOAc (3×). The aqueous layer was concentrated under reduced pressure and the resulting solid was treated with aqueous HCl. The solution was extracted with DCM (3×) and the combined organic layers were purified by flash chromatography, eluting with 0.5% TFA in iPrOH:CH2Cl2 (0:1→1:9) to give a white crystalline solid. (497 mg, 2.7 mmol, 28%). MS m/z=183 [M+H]+. Calculated for C8H10N2O3: 182.

Workup

  1. customthe reaction was quenched with saturated aq NH4Cl
  2. extractionextracted with EtOAc (3×)
  3. concentrationThe aqueous layer was concentrated under reduced pressure
  4. additionthe resulting solid was treated with aqueous HCl
  5. extractionThe solution was extracted with DCM (3×)
  6. customthe combined organic layers were purified by flash chromatography
  7. washeluting with 0.5% TFA in iPrOH:CH2Cl2 (0:1→1:9)
  8. customto give a white crystalline solid

Sources & evidence

ORD record
ord-f023f1e1f64140c9932d6d2f59958a10
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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