Picolinic acid → 3,5-dimethyl-1-(3-(2'-nitrobiphenyl-4-yloxy)phenyl)-1H-pyrazole

HRID 1509646Notes

Reaction equation

HRID 1509646 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([C:8]2[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=2)[N:3]=1.I[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[N+:28]([O-:30])=[O:29])=[CH:18][CH:17]=1.N1C=CC=CC=1C(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:16]3[CH:17]=[CH:18][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[N+:28]([O-:30])=[O:29])=[CH:20][CH:21]=3)[CH:9]=2)[N:3]=1

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 62657Potassium Phosphate, TribasicHCID 6297494'-Iodo-2-nitrobiphenylHCID 545258513-(3,5-Dimethyl-1H-pyrazol-1-yl)phenol

Product 1

HCID 1177297763,5-dimethyl-1-(3-(2'-nitrobiphenyl-4-yloxy)phenyl)-1H-pyrazoleYield 92%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-(3,5-dimethyl-1H-pyrazol-1-yl)phenol 2 (5.00 g, 26.56 mmol, 1.0 eq), 4′-iodo-2-nitrobiphenyl (10.38 g, 31.92 mmol, 1.2 eq), CuI (0.25 g, 1.33 mmol, 0.05 eq), picolinic acid (0.33 g, 2.66 mmol, 0.1 eq) and K3PO4 (11.28 g, 53.12 mmol, 2.0 eq) in DMSO (60 mL) was stirred at a temperature of 80-90° C. for three days under a nitrogen atmosphere, then cooled to ambient temperature. The solid was filtered off and washed with plenty of ethyl acetate (250 mL). The filtrate was washed with water three times and then dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified through column chromatography on silica gel using hexane/ethyl acetate (10:1-5:1-3:1) as an eluent to obtain the desired product as a sticky liquid (9.38 g in 92% yield). 1HNMR (DMSO-d6, 400 MHz): δ 2.15 (s, 3H), 2.30 (s, 3H), 6.06 (s, 1H), 7.07 (dd, J=8.0, 2.4 Hz, 1H), 7.13-7.16 (m, 3H), 7.30-7.32 (m, 1H), 7.36-7.40 (m, 2H), 7.52 (t, J=8.0, 1H), 7.57 (dd, J=7.6, 1.2 Hz, 1H), 7.59-7.64 (m, 1H), 7.75 (td, J=7.6, 1.2 Hz, 1H), 7.97 (dd, J=8.0, 1.2 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz): δ 12.30, 13.27, 107.63, 114.22, 117.18, 118.91, 118.97, 124.10, 128.81, 129.73, 130.61, 131.84, 132.28, 132.92, 134.33, 139.35, 141.11, 148.20, 148.92, 156.52, 156.67.

Workup

  1. temperaturecooled to ambient temperature
  2. filtrationThe solid was filtered off
  3. washwashed with plenty of ethyl acetate (250 mL)
  4. washThe filtrate was washed with water three times
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified through column chromatography on silica gel

Sources & evidence

ORD record
ord-1b6147d34ec643c8a5eed2734c576a7a
Source dataset
uspto-grants-2015_12
Patent number
US09224963B2

Reaction notes

Loading…