Water → 2-Nitro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile

HRID 872589

Reaction equation

HRID 872589 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.[O:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]1[N:19]1[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][CH:21]=[N:20]1.C(=O)([O-])[O-].[Na+].[Na+].O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[N+:10]([C:4]1[CH:3]=[C:2]([C:23]2[N:19]([CH:14]3[CH2:15][CH2:16][CH2:17][CH2:18][O:13]3)[N:20]=[CH:21][CH:22]=2)[CH:9]=[CH:8][C:5]=1[C:6]#[N:7])([O-:12])=[O:11]

Participants

7

Reactant 4

HCID 962Water2×HCID 10340Sodium CarbonateHCID 969244-Chloro-2-nitrobenzonitrileHCID 115872081-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 671715292-Nitro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrileYield 72.4%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-chloro-2-nitrobenzonitrile (15 g, 82 mmol) and 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (27.4 g, 99 mmol) in 300 ml of DMF were added bis(triphenylphosphine)palladium (II) chloride (1.12 g; 1.64 mmol), sodium carbonate (22.7 g; 0.16 mol) and water (30 ml). The reaction mixture was heated at 90° C. for 4.5 h, cooled and poured into 500 ml of water. The water phase was extracted twice with EtOAc, and the combined organic fractions were washed with saturated NaHCO3— solution and brine, dried over Na2SO4 and evaporated. The evaporation residual was suspended to EtOH (100 ml) and the remaining solids were filtered to give 17.7 g (72%) of the title compound. 1H-NMR (400 MHz; d6-DMSO): δ 1.52-1.68 (m, 3H), 1.78-1.87 (m, 1H), 1.91-2.00 (m, 1H), 2.31-2.47 (m, 1H), 3.67-3.76 (m, 1H), 3.99-4.06 (m, 1H), 5.32 (dd, 1H), 6.84 (d, 1H), 7.69 (d, 1H), 8.13 (dd, 1H), 8.32 (d, 1H), 8.60 (d, 1H).

Workup

  1. temperaturecooled
  2. extractionThe water phase was extracted twice with EtOAc
  3. washthe combined organic fractions were washed with saturated NaHCO3— solution and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. filtrationthe remaining solids were filtered

Sources & evidence

ORD record
ord-8733ec5d404f4503b23d1d61c2000b40
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Linked notes

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