1-Hexyne → 3,5-Diethyl-1-(3-hex-1-ynyl-phenyl)-1H-pyrazole-4-carboxylic acid methyl ester

HRID 1011866Notes

Reaction equation

HRID 1011866 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([CH2:19][CH3:20])=[N:7][N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14](Br)[CH:13]=2)[C:9]=1[CH2:10][CH3:11])=[O:4].[CH:21]#[C:22][CH2:23][CH2:24][CH2:25][CH3:26]>N1CCCCC1.[Cu]I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:6]([CH2:19][CH3:20])=[N:7][N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:21]#[C:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:13]=2)[C:9]=1[CH2:10][CH3:11])=[O:4]

Participants

6

Reactant 2

HCID 127321-HexyneHCID 673139921-(3-Bromo-phenyl)-3,5-diethyl-1H-pyrazole-4-carboxylic acid methyl ester2×

Product 1

HCID 673141873,5-Diethyl-1-(3-hex-1-ynyl-phenyl)-1H-pyrazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8082PiperidineSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 4.20 g (10.0 mmol) of 1-(3-bromo-phenyl)-3,5-diethyl-1H-pyrazole-4-carboxylic acid methyl ester (intermediate 1C) in 35 ml of piperidine was treated with 0.19 g (1.0 mmol) of copper(I)iodide and 1.16 g (1.0 mmol) of tetrakis-(triphenylphosphine)-palladium. The reaction mixture was warmed up to 60° C. and after 15 min, a solution of 0.82 g=1.00 ml (10.0 mmol) of hex-1-yne in 15 ml of piperidine was added drop by drop during 1 hour. After 30 min, the oil bath temperature was steadily increased to 80° C. The reaction mixture was then stirred at 80° C. for 4 hours, and subsequently cooled down to RT. The solvent was evaporated and the residue poured into crashed ice, acidified with HCl (37%) to pH 1-2 and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (n-heptane:EtOAc 1:0-9:1) to afford the title compound as light yellow oil. MS: 339.0 (MH+).

Workup

  1. temperaturethe oil bath temperature was steadily increased to 80° C
  2. temperaturesubsequently cooled down to RT
  3. customThe solvent was evaporated
  4. additionthe residue poured
  5. extractionextracted twice with EtOAc
  6. washthe organic phases were washed with water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by flash column chromatography (n-heptane:EtOAc 1:0-9:1)

Sources & evidence

ORD record
ord-136b20bce9594ee99e6b6b12daba7ba8
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

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