Piperazine → tert-butyl (2R)-4-ethyl-2-(piperazin-1-ylcarbonyl)piperazine-1-carboxylate

HRID 603189Notes

Reaction equation

HRID 603189 reaction equation
O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH3:34])[CH2:29][C@@H:28]1[C:35]([OH:37])=O)=[O:26])([CH3:23])([CH3:22])[CH3:21].[NH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>ClCCl>[CH2:33]([N:30]1[CH2:31][CH2:32][N:27]([C:25]([O:24][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:26])[C@@H:28]([C:35]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[O:37])[CH2:29]1)[CH3:34]

Participants

5

Reactant 3

HCID 4837PiperazineHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 59846012(2R)-1-(tert-butoxycarbonyl)-4-ethylpiperazine-2-carboxylic acid

Product 1

HCID 57656637tert-butyl (2R)-4-ethyl-2-(piperazin-1-ylcarbonyl)piperazine-1-carboxylateYield 50.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (253 mg, Acros chemicals) was added to a solution of (2R)-1-(tert-butoxycarbonyl)-4-ethylpiperazine-2-carboxylic acid (212 mg) in dry dichloromethane (6 ml) followed by addition on N-methyl morpholine (0.28 ml) and stirring under argon for 1 h piperazine (234 mg) was then added and stirring was continued for 18 h. Dichloromethane (30 ml) was added and extracted with 1M NaOH (2×10 mL). The organic layer was dried (MgSO4), filtered and evaporated. Purification by chromatography (5-50% MeOH:DCM) afforded the title compound (135 mg) as a foam

Workup

  1. additionfollowed by addition on N-methyl morpholine (0.28 ml)
  2. additionwas then added
  3. extractionextracted with 1M NaOH (2×10 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by chromatography (5-50% MeOH:DCM)

Sources & evidence

ORD record
ord-b181a771c2524359a5479a9a8da3a196
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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