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

HRID 526748Notes

Reaction equation

HRID 526748 reaction equation
I[C:2]1[C:6]([CH:7]=[O:8])=[CH:5][N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:3]=1.[CH3:15][CH:16]([O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)[CH3:17].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:16]([O:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[C:6]([CH:7]=[O:8])=[CH:5][N:4]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[N:3]=2)=[CH:21][CH:20]=1)([CH3:17])[CH3:15]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 36987264-Isopropoxybenzeneboronic acidHCID 904242893-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carbaldehyde

Product 1

HCID 1176662103-(4-Isopropoxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazole-4-carbaldehydeYield 73%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
98 °C

Procedure

A mixture of 3-iodo-1-(oxan-2-yl)-1H-pyrazole-4-carbaldehyde (6 g, 19.60 mmol, 1.00 equiv), [4-(propan-2-yloxy)phenyl]boronic acid (7.0 g, 38.89 mmol, 1.98 equiv), Pd(PPh3)4 (2.2 g, 1.90 mmol, 0.10 equiv) and sodium carbonate (6.2 g, 58.50 mmol, 2.98 equiv) in toluene (60 mL) and water (5 mL) was stirred under nitrogen at 98° C. overnight. The reaction was cooled to room temperature then diluted with 600 mL of ethyl acetate. The resulting mixture was washed with 3×300 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 3.0-6.5% ethyl acetate in petroleum ether to give 4.5 g (73%) of 3-(4-isopropoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carbaldehyde as yellow oil. 1H NMR (300 MHz, CDCl3) δ: 9.98 (s, 1H), 8.23 (s, 1H), 7.70-7.65 (m, 2H), 7.26 (s, 1H), 6.98-6.93 (m, 2H), 5.45-5.41 (m, 1H), 4.65-4.57 (m, 1H), 4.13-4.09 (m, 1H), 3.78-3.73 (m, 1H), 2.21-2.03 (m, 3H), 1.71-1.63 (m, 3H), 1.36 (d, J=6.0 Hz, 6H) ppm. LCMS (method D, ESI): RT=1.57 min, m/z=315.0 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. washThe resulting mixture was washed with 3×300 mL of brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified on a silica gel column
  6. washeluted with 3.0-6.5% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-229cd31268f340f3a0125eb506c37425
Source dataset
uspto-grants-2016_05
Patent number
US09346761B2

Reaction notes

Loading…