5-Bromothiophene-2-carbaldehyde → Tert-butyl 4-(5-formylthiophen-2-yl)piperazine-1-carboxylate

HRID 16745

Reaction equation

HRID 16745 reaction equation
Br[C:2]1[S:6][C:5]([CH:7]=[O:8])=[CH:4][CH:3]=1.[N:9]1([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(C(C)C)C(C)C)C>CS(C)=O>[CH:7]([C:5]1[S:6][C:2]([N:12]2[CH2:11][CH2:10][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13]2)=[CH:3][CH:4]=1)=[O:8]

Participants

5

Reactant 3

HCID 784285-Bromothiophene-2-carbaldehydeHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 28065298Tert-butyl 4-(5-formylthiophen-2-yl)piperazine-1-carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 5-bromothiophene-2-carboxaldehyde (3.82 g, 20.0 mmol), tert-butyl piperazine-1-carboxylate (4.1 g, 22.0 mmol), N-ethyl-N,N-diisopropylamine (7.0 ml, 40.0 mmol) and dimethylsulphoxide (5.0 ml) were stirred at 130° C. under an atmosphere of nitrogen for 18 h. The cooled mixture was partitioned between ethyl acetate and water. The organics were washed with water, brine, dried over magnesium sulphate and evaporated. The resultant dark red solid was purified by silica column chromatography, eluting with dichloromethane followed by ethyl acetate/dichloromethane (15%) to give tert-butyl 4-(5-formylthien-2-yl)piperazine-1-carboxylate (4.3 g, 73%).

Workup

  1. customThe cooled mixture was partitioned between ethyl acetate and water
  2. washThe organics were washed with water, brine
  3. dry with materialdried over magnesium sulphate
  4. customevaporated
  5. customThe resultant dark red solid was purified by silica column chromatography
  6. washeluting with dichloromethane

Sources & evidence

ORD record
ord-c417a6ea2d5f4f54842f9fa9a25eed89
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Linked notes

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