Cesium carbonate → Ethyl 5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxylate

HRID 1911415Notes

Reaction equation

HRID 1911415 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=1.[CH3:12][C:13]1([CH3:19])[CH2:18][NH:17][CH2:16][CH2:15][NH:14]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:12][C:13]1([CH3:19])[NH:14][CH2:15][CH2:16][N:17]([C:2]2[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=2)[CH2:18]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 605723Ethyl 5-bromothiophene-2-carboxylateHCID 634876Binap, (A+-)-HCID 146641862,2-Dimethylpiperazine

Product 1

HCID 66589679Ethyl 5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxylateYield 36.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Palladium(II) acetate (0.112 g, 0.50 mmol) was added to ethyl 5-bromothiophene-2-carboxylate (1.175 g, 5 mmol), 2,2-dimethyl-piperazine (0.571 g, 5.00 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.311 g, 0.50 mmol) and cesium carbonate (2.281 g, 7.00 mmol) in toluene (50.0 ml) at 20° C. under nitrogen. The resulting suspension was stirred at 110° C. for 23 h. The crude product was purified by ion exchange chromatography, using a SCX2 column. The crude material was dissolved in methanol and then applied to the column. The desired product was eluted from the column using 2M NH3 in methanol and pure fractions were evaporated to dryness to afford the crude product as a brown solid. This material was further purified by silica column chromatography, eluting with a gradient of 0 to 4% MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxylate (0.484 g, 36.1%) as a brown gum.

Workup

  1. customThe crude product was purified by ion exchange chromatography
  2. dissolutionThe crude material was dissolved in methanol
  3. washThe desired product was eluted from the column
  4. customwere evaporated to dryness
  5. customto afford the crude product as a brown solid
  6. customThis material was further purified by silica column chromatography
  7. washeluting with a gradient of 0 to 4% MeOH in DCM
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-73b9767268854222ab628cce72d8e7d3
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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