Ethylene Glycol → 1-Boc-4-(2-thienyl)piperazine

HRID 1670743

Reaction equation

HRID 1670743 reaction equation
I[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].C(O)CO.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.C(OCC)(=O)C.CC(O)C>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:2]2[S:3][CH:4]=[CH:5][CH:6]=2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

8

Reactant 4

HCID 174Ethylene GlycolHCID 189212-IodothiopheneHCID 62657Potassium Phosphate, TribasicHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 673439001-Boc-4-(2-thienyl)piperazineYield 77%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-iodothiophene (Aldrich Co., 1.0 g), 1-(tert-butoxycarbonyl)piperazine (Aldrich Co. (hereafter the same), 1.06 g), copper(I) iodide (45 mg), ethylene glycol (530 μl), potassium phosphate (2.02 g) and 2-propanol (5 ml) was heated under reflux for 20 hr. Ethyl acetate was added, and the mixture was filtered through a Celite (trademark) filter. The filtrate was washed 3 times with 28% aqueous ammonia, and then washed with saturated brine. The solvent was evaporated under reduced pressure to give a brown solid. The solid was purified by silica gel column chromatography (elution solvent: ethyl acetate-hexane (7:3)) to give 4-(2-thienyl)piperazine-1-carboxylic acid tert-butyl ester (984 mg, yield 77%).

Workup

  1. temperatureunder reflux for 20 hr
  2. filtrationthe mixture was filtered through a Celite (trademark)
  3. filtrationfilter
  4. washThe filtrate was washed 3 times with 28% aqueous ammonia
  5. washwashed with saturated brine
  6. customThe solvent was evaporated under reduced pressure
  7. customto give a brown solid
  8. customThe solid was purified by silica gel column chromatography (elution solvent: ethyl acetate-hexane (7:3))

Sources & evidence

ORD record
ord-ffc748b1030f4f6abf2f239762f169db
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Linked notes

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