tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-(thiazol-5-ylmethyl)piperazine-1-carboxylate

HRID 416929Notes

Reaction equation

HRID 416929 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[S:14]1[C:18]([CH:19]=O)=[CH:17][N:16]=[CH:15]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[S:14]1[C:18]([CH2:19][N:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]2)=[CH:17][N:16]=[CH:15]1

Participants

5

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 27735771,3-Thiazole-5-carbaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 57897199tert-Butyl 4-(thiazol-5-ylmethyl)piperazine-1-carboxylateYield 51.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

N-Boc-piperazine (0.900 g, 4.86 mmol, 1.1 eq) was dissolved in 1,2-DCE (12 mL). To this solution, 5-thiazolecarboxaldehyde (0.500 g, 4.42 mmol, 1 eq) in 1,2-DCE (2 mL) was added followed by the portionwise addition of sodium triacetoxyborohydride (1.310 g, 6.19 mmol, 1.4 eq). The reaction mixture was stirred at room temperature for 17 h and then washed with a saturated aqueous solution of NaHCO3. The organic layer was dried (MgSO4), the solvent removed in vacuo and the crude product was purified by column chromatography on a Biotage SP1 system (DCM/EtOAc; v/v 1:1) to give the title compound as a light yellow oil (0.640 g, 51%); 1H-NMR (500 MHz, CDCl3): δ 1.46 (s, 9H, C(CH3)3), 2.43 (t, J=4.5 Hz, 4H, piperazine N(CH2)2), 3.44 (t, J=5.0 Hz, 4H, piperazine N(CH2)2), 3.77 (s, 2H, NCH2), 7.72 (s, 1H, thiazole 4-H), 8.76 (s, 1H, thiazole 2-H); LC (Method B)-MS (ESI, m/z): Rt=2.04 min—284 [(M+H)+, 100%].

Workup

  1. washwashed with a saturated aqueous solution of NaHCO3
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe solvent removed in vacuo
  4. customthe crude product was purified by column chromatography on a Biotage SP1 system (DCM/EtOAc; v/v 1:1)

Sources & evidence

ORD record
ord-5470d7558f4d4170b11c5fb783f91521
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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