p-Fluoronitrobenzene → HCID 90461069, compound

HRID 1053644Notes

Reaction equation

HRID 1053644 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[OH:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1)[N:16]=[C:15]2[CH:27]=[O:28].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([O:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[N:17]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[N:16]=[C:15]3[CH:27]=[O:28])=[CH:3][CH:4]=1)([O-:10])=[O:9]

Participants

6

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 10796Cesium carbonateHCID 90460860HCID 90460860, compound

Product 1

HCID 90461069HCID 90461069, compoundYield 78.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-fluoro-4-nitrobenzene (258 mg, 1.83 mmol, 1.00 equiv), (R/S) 5-hydroxy-1-(oxan-2-yl)-1H-indazole-3-carbaldehyde (300 mg, 1.22 mmol, 0.67 equiv) and Cs2CO3 (1.2 g, 3.68 mmol, 2.01 equiv) in 1,4-dioxane (25 mL) was stirred at 100° C. for 4 h. The reaction mixture was cooled to room temperature and then diluted with 50 mL of H2O. The resulting mixture was extracted with 3×200 mL of ethyl acetate. The combined organic layers was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-13% of ethyl acetate in petroleum ether to give 350 mg (52%) of (R/S) 5-(4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde as a light yellow solid. 1H-NMR (300 MHz, CDCl3): δ 10.3 (s, 1H), 8.23-8.18 (m, 2H), 8.01 (s, 1H), 7.78-7.75 (m, 1H), 7.27-7.23 (m, 1H), 7.04-7.00 (m, 1H), 5.89-5.85 (m, 1H), 4.06-4.01 (m, 1H), 3.85-3.77 (m, 1H), 2.60-2.52 (m, 1H), 2.21-2.17 (m, 2H), 1.86-1.74 (m, 3H) ppm.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe resulting mixture was extracted with 3×200 mL of ethyl acetate
  3. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified on a silica gel column
  6. washeluted with 0-13% of ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-aae5b0d563ef4ae6ab0f026decf63616
Source dataset
uspto-grants-2016_07
Patent number
US09394258B2

Reaction notes

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