Triethylamine → 1-(3-Biphenyl-3-yl-1,1-dimethylprop-2-yn-1-yl)-4-(2,2-dimethylpropanoyl)piperazine

HRID 1008866Notes

Reaction equation

HRID 1008866 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:14][C:15]([CH3:30])([CH3:29])[C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24]([CH3:28])([CH3:27])[C:25]#[CH:26])[CH2:20][CH2:19]1)=[O:17].C(N(CC)CC)C>O1CCCC1.C(OCC)(=O)C.[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>[C:4]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=[C:2]([C:26]#[C:25][C:24]([N:21]2[CH2:20][CH2:19][N:18]([C:16](=[O:17])[C:15]([CH3:30])([CH3:29])[CH3:14])[CH2:23][CH2:22]2)([CH3:28])[CH3:27])[CH:3]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 164493-BromobiphenylHCID 866102081-(2,2-Dimethylpropanoyl)-4-(1,1-dimethylprop-2-yn-1-yl)piperazine

Product 1

HCID 673057591-(3-Biphenyl-3-yl-1,1-dimethylprop-2-yn-1-yl)-4-(2,2-dimethylpropanoyl)piperazineYield 61.7%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 10122028Bis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

1.05 g (4.5 mmol) of 3-bromobiphenyl and 0.9 g (3.6 mmol) of 1-(2,2-dimethylpropanoyl)-4-(1,1-dimethylprop-2-yn-1-yl)piperazine, prepared in step 5.1., 0.75 ml (5.38 mmol) of triethylamine and 0.028 g (0.11 mmol) of triphenylphosphine are dissolved in 8 ml of tetrahydrofuran. Under an argon atmosphere, 0.126 g (0.18 mmol) of the dichloride complex of bis(triphenylphosphine) palladium is added. The mixture is stirred for 15 minutes and then 0.014 g (0.07 mmol) of cuprous iodide is added. The mixture is stirred at ambient temperature for 4 hours and then at 60° C. overnight. After cooling to temperature it is diluted with 25 ml of ethyl acetate and filtered on paper. The solid is rinsed with 4 times 10 ml of ethyl acetate. 4 g of silica are added to the filtrate, which is evaporated to dryness. The residue is purified by chromatography on silica gel, eluting with a 90/10 then 80/20 and 70/30 mixture of cyclohexane and ethyl acetate, to give 0.90 g (2.22 mmol) of product in the form of a orange-colored oil.

Workup

  1. stirringThe mixture is stirred at ambient temperature for 4 hours
  2. customat 60° C.
  3. customovernight
  4. temperatureAfter cooling to temperature it
  5. filtrationfiltered on paper
  6. washThe solid is rinsed with 4 times 10 ml of ethyl acetate
  7. addition4 g of silica are added to the filtrate, which
  8. customis evaporated to dryness
  9. customThe residue is purified by chromatography on silica gel
  10. washeluting with a 90/10
  11. addition80/20 and 70/30 mixture of cyclohexane and ethyl acetate

Sources & evidence

ORD record
ord-72c1a8ef385746afa76eeaa09f3a3efc
Source dataset
uspto-grants-2011_07
Patent number
US07973042B2

Reaction notes

Loading…