Water → 5-(5-fluoro-2-methoxyphenyl)-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazol-4-amine

HRID 1466632Notes

Reaction equation

HRID 1466632 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][CH3:25])=[C:6]([C:8]2[N:12]([CH2:13][CH2:14][O:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:11]=[CH:10][C:9]=2[N+:21]([O-])=O)[CH:7]=1.O.[Cl-].[NH4+]>C(O)C.ClCCl.[Fe]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][CH3:25])=[C:6]([C:8]2[N:12]([CH2:13][CH2:14][O:15][CH2:16][Si:17]([CH3:18])([CH3:20])[CH3:19])[N:11]=[CH:10][C:9]=2[NH2:21])[CH:7]=1

Participants

7

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 668509485-(5-fluoro-2-methoxyphenyl)-4-nitro-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazole

Product 1

HCID 668506985-(5-fluoro-2-methoxyphenyl)-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazol-4-amineYield 70.2%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 5-(5-fluoro-2-methoxyphenyl)-4-nitro-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazole (1.0 g, 2.7 mmol) in 8 mL ethanol was added 16 mL water, ammonium chloride (570 mg, 10.8 mmol), and iron powder (760 mg, 13.5 mmol). The reaction mixture was stirred at 75° C. for 6 hours. After cooling to room temperature, the reaction was diluted with dichloromethane and filtered through a celite pad, rinsing with more dichloromethane. The filtrate was added to 150 mL saturated aqueous sodium bicarbonate and extracted twice with dichloromethane. The combined organic extracts were dried over magnesium sulfate and concentrated to yield 640 mg (70%) of 5-(5-fluoro-2-methoxyphenyl)-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazol-4-amine, which was carried forward without purification. LCMS (ESI) m+H=338.1. 1H NMR (400 MHz, CDCl3) δ: 7.37 (m, 2H), 7.20 (t, 1H), 7.04 (dd, 1H), 5.42 (t, 2H), 3.90 (d, 3H), 3.65 (t, 2H), 0.96 (t, 2H), 0 (s, 9H).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationfiltered through a celite pad
  3. washrinsing with more dichloromethane
  4. additionThe filtrate was added to 150 mL saturated aqueous sodium bicarbonate
  5. extractionextracted twice with dichloromethane
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a25630875c634e4c8c66b4041eed5639
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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