Pivalic acid → HCID 66851308, compound

HRID 1466579Notes

Reaction equation

HRID 1466579 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][N:7]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[CH:8]=1)([O-:3])=[O:2].Br[C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[O:25][CH3:26].C(=O)([O-])[O-].[K+].[K+].CC(C)(C)C(O)=O>CN(C)C(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2.C(OCC)(=O)C>[Cl:24][C:22]1[CH:21]=[CH:20][C:19]([O:25][CH3:26])=[C:18]([C:5]2[C:4]([N+:1]([O-:3])=[O:2])=[CH:8][N:7]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:6]=2)[CH:23]=1

Participants

9

Reactant 4

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 5219352-Bromo-4-chloroanisoleHCID 584056874-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

Product 1

HCID 66851308HCID 66851308, compoundYield 100%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (4.26 g, 17.5 mmol) in 40 mL N,N-dimethylacetamide was added 2-bromo-4-chloroanisole (3.35 mL, 24.6 mmol), palladium (II) acetate (197.2 mg, 0.878 mmol), di(1-adamantyl)-n-butylphosphine (469.5 mg, 1.309 mmol), potassium carbonate (7.27 g, 52.6 mmol), and trimethylacetic acid (0.452 g, 4.43 mmol). While stirring at room temperature, nitrogen gas was bubbled through the reaction mixture for 10 minutes, and the reaction then heated at 120° C. for 6 hours. The reaction was then cooled to room temperature, diluted into ethyl acetate, and washed with water and brine, dried over magnesium sulfate and concentrated. The crude material was purified by flash chromatography on silica gel (0 to 25% ethyl acetate in heptanes) to obtain 6.719 g (89%) of 3-(5-chloro-2-methoxyphenyl)-4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole. LCMS (ESI) m+H=384.2; 1H NMR (400 MHz, CDCl3) δ: 8.22 (s, 1H), 7.46 (d of d, 1H), 7.36 (d, 1H), 6.95 (d, 1H), 5.23 (m, 2H), 3.56 (m, 2H), 0.87 (m, 2H).

Workup

  1. customnitrogen gas was bubbled through the reaction mixture for 10 minutes
  2. customthe reaction
  3. temperaturethen heated at 120° C. for 6 hours
  4. temperatureThe reaction was then cooled to room temperature
  5. washwashed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe crude material was purified by flash chromatography on silica gel (0 to 25% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-ffe54ef4d31e41fcae6fc2ae6da47e27
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

Loading…