Trifluoroacetic acid → Tert-butyl 4-[2-(aminomethyl)phenyl]piperazine-1-carboxylate

HRID 1592733Notes

Reaction equation

HRID 1592733 reaction equation
[BH4-].[Na+].C(O)(C(F)(F)F)=O.[C:10]([N:17]1[CH2:22][CH2:21][N:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]#[N:30])[CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11]>C1COCC1>[C:10]([N:17]1[CH2:18][CH2:19][N:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH2:29][NH2:30])[CH2:21][CH2:22]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 4311764Sodium borohydrideHCID 18388395tert-Butyl 4-(2-cyanophenyl)piperazine-1-carboxylate

Product 1

HCID 4961274Tert-butyl 4-[2-(aminomethyl)phenyl]piperazine-1-carboxylateYield 30.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2-cyano-phenyl)-piperazine (2.4 g, 12.78 mmol) in THF and H2O (25 mL, 1:1) was added K2CO3 (3.9 g, 28.12 mmol). The solution was allowed to stir for about 10 minutes at r.t. Boc-anhydride (3.1 g, 14.06 mmol) was then added and reaction was allowed to stir for 1 h. The reaction mixture was diluted with EtOAc (100 mL) and washed with sat. NaHCO3 (100 mL) and brine (100 mL). The organic phase was concentrated to dryness yielding 3.2 g of 1-Boc-4-(2-cyano-phenyl)-piperazine (88%). To a solution of sodium borohydride (2.1 g, 56.03 mmol) in THF (25 mL) at 0° C. was added TFA (4.3 mL, 56.03 mmol) dropwise. 1-Boc-4-(2-cyano-phenyl)-piperazine (3.2 g, 11.21 mmol) was then added slowly at r.t. The reaction was allowed to stir for about 12 hours at r.t. The reaction was quenched with H2O, diluted five-fold with EtOAc and washed with brine. The organic phase was concentrated to dryness yielding about 1.0 g of 1-Boc-4-(2-aminomethyl-phenyl)-piperazine (30%). MS (ESI+) 292.1 (M+1)

Workup

  1. customThe reaction was quenched with H2O
  2. additiondiluted five-fold with EtOAc
  3. washwashed with brine
  4. concentrationThe organic phase was concentrated to dryness

Sources & evidence

ORD record
ord-98bdebc7cbfa41e3aa6d2eb28867b038
Source dataset
uspto-grants-2007_11
Patent number
US07291619B2

Reaction notes

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