Potassium Carbonate → 4-(4-(2-fluorophenoxy)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-3-carbaldehyde

HRID 526780Notes

Reaction equation

HRID 526780 reaction equation
I[C:2]1[C:3]([CH:13]=[O:14])=[N:4][N:5]([CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)[CH:6]=1.C(=O)([O-])[O-].[K+].[K+].[F:21][C:22]1[CH:43]=[CH:42][CH:41]=[CH:40][C:23]=1[O:24][C:25]1[CH:30]=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][CH:26]=1>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:21][C:22]1[CH:43]=[CH:42][CH:41]=[CH:40][C:23]=1[O:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[C:3]([CH:13]=[O:14])=[N:4][N:5]([CH:7]3[CH2:12][CH2:11][CH2:10][CH2:9][O:8]3)[CH:6]=2)=[CH:27][CH:26]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 579753882-(4-(2-Fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 904606424-iodo-1-(oxan-2-yl)-1H-pyrazole-3-carbaldehyde

Product 1

HCID 1176659354-(4-(2-fluorophenoxy)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-3-carbaldehydeYield 59%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-iodo-1-(oxan-2-yl)-1H-pyrazole-3-carbaldehyde (227 mg, 0.74 mmol, 1.00 equiv), Pd(dppf)Cl2 (54 mg, 0.07 mmol, 0.10 equiv), potassium carbonate (304 mg, 2.20 mmol, 2.97 equiv) and 2-[4-(2-fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (280 mg, 0.89 mmol, 1.20 equiv) in 1,4-dioxane (20 mL) and water (2 mL) was stirred under nitrogen at 100° C. overnight. The resulting mixture was cooled to room temperature and concentrated under vacuum. The residue was purified on a silica gel column eluted with 1-9% ethyl acetate in petroleum ether to give 160 mg (59%) of 4-(4-(2-fluorophenoxy)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-3-carbaldehyde as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 9.91 (s, 1H), 7.91 (s, 1H), 7.60 (d, J=2.1 Hz, 2H), 7.57-7.43 (m, 1H), 7.43-7.40 (m, 3H), 7.03 (d, J=2.1 Hz, 2H), 6.14-6.10 (m, 1H), 4.00-3.99 (m, 1H), 3.68-3.66 (m, 1H), 2.30-2.28 (m, 1H), 1.98-1.93 (m, 2H), 1.56-1.55 (m, 2H), 1.19-1.17 (m, 1H) ppm. LCMS (method D, ESI): RT=1.78 min, m/z=367.0 [M+H]+.

Workup

  1. temperatureThe resulting mixture was cooled to room temperature
  2. concentrationconcentrated under vacuum
  3. customThe residue was purified on a silica gel column
  4. washeluted with 1-9% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-eec8932904b540cb8f3c6153c91bb1ac
Source dataset
uspto-grants-2016_05
Patent number
US09346761B2

Reaction notes

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