Ammonium Chloride → 6-(2,4-Difluorophenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1,4-dihydro-pyrazolo[4,3-b]pyridin-5-one

HRID 2114555Notes

Reaction equation

HRID 2114555 reaction equation
C[O:2][C:3](=O)[CH:4]([O:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=1[F:31])[CH:5](O)[C:6]1[N:7]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:8]=[CH:9][C:10]=1[N+:11]([O-])=O.[Cl-].[NH4+]>C(O)C.O.[Fe]>[F:31][C:25]1[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:24]=1[O:23][C:4]1[C:3](=[O:2])[NH:11][C:10]2[CH:9]=[N:8][N:7]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=2[CH:5]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 598129592-(2,4-difluorophenoxy)-3-hydroxy-3-[4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazol-3-yl]propionic acid methyl ester

Product 1

HCID 598129756-(2,4-Difluorophenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1,4-dihydro-pyrazolo[4,3-b]pyridin-5-oneYield 94.3%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

To a solution of 2-(2,4-difluorophenoxy)-3-hydroxy-3-[4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazol-3-yl]propionic acid methyl ester (125 mg, 0.264 mmol) in ethanol (2 mL) and water (1 mL) was added ammonium chloride (74 mg, 5.2 eq) followed by iron powder (Fisher Brand, Electrolytic). The resulting mixture was stirred at room temperature for 45 minutes, refluxed overnight, cooled to room temperature, diluted with ethanol, and filtered through a 3 cm bed of celite with additional ethanol. The filtrate was concentrated, and the residue was diluted with ethyl acetate (80 mL) and water (40 mL). The organic layer was separated, washed with water (2×40 mL) and brine (1×40 mL), dried over magnesium sulfate, filtered and concentrated to give the title compound as a thick tan oil (98 mg, (M+H)+=394).

Workup

  1. temperaturerefluxed overnight
  2. temperaturecooled to room temperature
  3. filtrationfiltered through a 3 cm bed of celite with additional ethanol
  4. concentrationThe filtrate was concentrated
  5. additionthe residue was diluted with ethyl acetate (80 mL) and water (40 mL)
  6. customThe organic layer was separated
  7. washwashed with water (2×40 mL) and brine (1×40 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b006a1c7cec5442db9e5b23244302f5a
Source dataset
uspto-grants-2008_10
Patent number
US07435731B2

Reaction notes

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