Potassium Carbonate → 1-({5-Chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-4-nitro-1H-pyrazole

HRID 1746102Notes

Reaction equation

HRID 1746102 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C=O)C.[I-].[Na+]>[Cl:23][C:21]1[CH:20]=[CH:19][C:18]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[C:17]([CH2:16][N:6]2[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:8]=[N:7]2)[CH:22]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 163764-nitro-1H-pyrazoleHCID 221055531-(Benzyloxy)-2-(bromomethyl)-4-chlorobenzene2×

Product 1

HCID 866927341-({5-Chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-4-nitro-1H-pyrazoleYield 86.2%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-nitropyrazole (Manchester organics; 0.503 g, 4.45 mmol) in DMF (10 ml) was added potassium carbonate (1.24 g, 9.0 mmol), sodium iodide (24 mg, 0.160 mmol) and then 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (synthesised according to WO2006066968; 1.23 g, 3.95 mmol). The reaction was stirred at ambient temperature overnight. A further amount of 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (156 mg) was added and the reaction was stirred at ambient temperature for a further 30 min. The reaction mixture was concentrated in vacuo and treated with water (60 ml). The aqueous solution was extracted with ethyl acetate (3×60 ml). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The sample was loaded in dichloromethane and purified on silica (50 g) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound (1.17 g) as a white solid; LCMS (System 1): MH+=344, tRET=3.58 min.

Workup

  1. stirringthe reaction was stirred at ambient temperature for a further 30 min
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additiontreated with water (60 ml)
  4. extractionThe aqueous solution was extracted with ethyl acetate (3×60 ml)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. custompurified on silica (50 g)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-e40d11b53e8e4596963f996d8e2b0ab5
Source dataset
uspto-grants-2015_10
Patent number
US09149462B2

Reaction notes

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