Diisopropylethylamine → 1-(4-ethynylbenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester

HRID 1500400Notes

Reaction equation

HRID 1500400 reaction equation
[C:1]([O:5][C:6](=[O:23])[CH2:7][C:8]1[C:9]([CH3:22])=[N:10][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=2)[C:12]=1[CH3:13])([CH3:4])([CH3:3])[CH3:2].[CH:24](N(C(C)C)CC)(C)[CH3:25].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:1]([O:5][C:6](=[O:23])[CH2:7][C:8]1[C:9]([CH3:22])=[N:10][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:24]#[CH:25])=[CH:17][CH:16]=2)[C:12]=1[CH3:13])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 68390870tert-butyl 2-(1-(4-iodobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetate

Product 1

HCID 867165361-(4-ethynylbenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 1-(4-iodobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester (12.2 g) in tetrahydrofuran (100 ml) at room temperature is added diisopropylethylamine (12.3 ml). The solution is degassed and put under argon. Ethynyltrimethylsilane (4.5 ml), copper(I)iodide (543 mg) and bis-(triphenylphosphine)-palladiumdichloride (1.0 g) are added. After 15 h of stirring, the reaction is absorbed onto Extrelute and purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate) to yield a solid (10.7 g; [M+H]=397; HPLC retention time 1.71 min (Method J)). The solid is dissolved in tetrahydrofuran (200 ml) and is stirred together with tetrabutylammonium fluoride (1 M in THF, 28 ml). After 15 h at room temperature, the reaction mixture is concentrated in vacuo. The residue is purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate) to yield 1-(4-ethynylbenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester (6.8 g; [M+H]=325; HPLC retention time 1.47 min (Method J)).

Workup

  1. customThe solution is degassed
  2. additionEthynyltrimethylsilane (4.5 ml), copper(I)iodide (543 mg) and bis-(triphenylphosphine)-palladiumdichloride (1.0 g) are added
  3. customthe reaction is absorbed onto Extrelute
  4. custompurified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate)
  5. customto yield a solid (10.7 g; [M+H]=397; HPLC retention time 1.71 min (Method J))
  6. waitAfter 15 h at room temperature
  7. concentrationthe reaction mixture is concentrated in vacuo
  8. customThe residue is purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate)

Sources & evidence

ORD record
ord-ceb58efe395445e0ab7fa5eb155f8599
Source dataset
uspto-grants-2015_12
Patent number
US09206164B2

Reaction notes

Loading…