Hydrochloric Acid → 4-(2-Fluoro-4-nitrophenoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-ol

HRID 2117093Notes

Reaction equation

HRID 2117093 reaction equation
C([O:7][C:8]1[C:9]([CH3:28])=[C:10]2[N:15]([CH:16]=1)[N:14]=[CH:13][N:12]=[C:11]2[O:17][C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=1[F:27])(=O)C(C)(C)C.[OH-].[Na+].Cl>C(O)C>[F:27][C:19]1[CH:20]=[C:21]([N+:24]([O-:26])=[O:25])[CH:22]=[CH:23][C:18]=1[O:17][C:11]1[C:10]2=[C:9]([CH3:28])[C:8]([OH:7])=[CH:16][N:15]2[N:14]=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 210816484-(2-Fluoro-4-nitrophenoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl pivalate

Product 1

HCID 210816464-(2-Fluoro-4-nitrophenoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-olYield 53%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a heterogeneous mixture of 4-(2-fluoro-4-nitrophenoxy)-5-methylpyrrolo[2,1-f][1,2,4]-triazin-6-yl pivalate (1.45 g, 3.74 mmol) in absolute ethanol (19 mL), at room temperature under a nitrogen atmosphere, was added 1 N aqueous sodium hydroxide. The reaction mixture was stirred at ambient temperature for 1.5 h before being neutralized to pH 7 with 1 N aqueous hydrochloride. The reaction mixture was concentrated to remove ethanol, before being partitioned between ethyl acetate and water. The aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were washed twice with water, once with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated in vacuo. Purification by silica gel (Merck KGaA, 230-400 mesh particle size) flash chromatography, eluting with 2:1 hexane/ethyl acetate, afforded the title compound (602 mg, 53% for Steps A-B) as a yellow solid. 1H NMR (CDCl3) δ 8.20-8.12 (m, 2H), 7.84 (s, 1H), 7.58-7.53 (m, 1H), 7.53 (s, 1H), 4.76 (s, 1H), 2.48 (s, 3H); MS(ESI+) m/z 305.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto remove ethanol
  3. custombefore being partitioned between ethyl acetate and water
  4. extractionThe aqueous layer was extracted twice with ethyl acetate
  5. washThe combined organic extracts were washed twice with water, once with saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel (Merck KGaA, 230-400 mesh particle size) flash chromatography
  9. washeluting with 2:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-e92377a58c5441eca86e4824c717bf2f
Source dataset
uspto-grants-2008_10
Patent number
US07439246B2

Reaction notes

Loading…