Cesium carbonate → 4-[2-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-benzonitrile

HRID 2261756Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13]([CH2:14][OH:15])=[C:12]([CH:16]([CH3:18])[CH3:17])[CH:11]=[N:10]1.F[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([CH3:28])[CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[N:9]1[C:13]([CH2:14][O:15][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([CH3:28])[CH:21]=2)=[C:12]([CH:16]([CH3:18])[CH3:17])[CH:11]=[N:10]1

Participants

Conditions

Temperature: 80 °C

Procedure

To an ambient temperature solution of [2-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-yl]-methanol (2.50 g, 8.76 mmol) in DMF (15 mL) is added 4-Fluoro-2-methyl-benzonitrile 1.18 g, 8.76 mmol), cesium carbonate (5.71 g, 17.53 mmol). The reaction mixture is heated to 80° C. overnight. The reaction mixture is concentrated and the residue is partitioned between Et2O and water. The aqueous layer is extracted with Et2O and the combined organic layers are washed with brine, dried (MgSO4), filtered, concentrated, and chromatographed (0% to 20% EtOAc/Hex) to yield the title compound (2.13 g, 61%). 1H NMR (400 MHz, CDCl3) δ 7.72 (s, 1H), 7.46-7.40 (m, 3H), 7.32 (dd, 1H, J=9.0, 7.3 Hz), 6.68-6.62 (m, 2H), 4.85 (s, 2H), 2.99 (sept, 1H, J=7.0 Hz), 2.46 (s, 3H), 1.31 (d, 6H, J=7.0 Hz).

Workup

concentrationThe reaction mixture is concentrated
customthe residue is partitioned between Et2O and water
extractionThe aqueous layer is extracted with Et2O
washthe combined organic layers are washed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
customchromatographed (0% to 20% EtOAc/Hex)

Sources & evidence

ORD record: ord-84c3b8eceec94005bfa1a38e6b3ee970
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07846960B2

Reaction notes

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