tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(pyrimidin-5-ylmethyl)piperazine-1-carboxylate

HRID 416855Notes

Reaction equation

HRID 416855 reaction equation
[N:1]1[CH:6]=[C:5]([CH:7]=O)[CH:4]=[N:3][CH:2]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C([BH3-])#N.[Na+]>C(O)C.C(O)(=O)C>[N:3]1[CH:4]=[C:5]([CH2:7][N:19]2[CH2:18][CH2:17][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH2:21][CH2:20]2)[CH:6]=[N:1][CH:2]=1

Participants

6

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 2761034Pyrimidine-5-carboxaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 46867017Tert-butyl 4-(pyrimidin-5-ylmethyl)piperazine-1-carboxylateYield 55.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

A solution of pyrimidine 5-carboxaldehyde (100 mg, 0.92 mmol) in ethanol (2 mL) and acetic acid (0.2 mL) at room temperature was treated with tert-butyl-1-piperazine carboxylate (2.5 eq, 2.31 mmol, 430 mg) and stirred for 5 minutes. Sodium cyanoborohydride (0.95 eq, 0.88 mmol, 55 mg) was added portionwise and the reaction then stirred for 16 h. Concentration in vacuo and preparative tlc purification (EtOAc) gave the product (141 mg, 55%) as a pale yellow oil; δH (500 MHz, CDCl3) 1.47 (s, 9H, C(CH3)3), 1.95 (br, 2H, piperazine NCH2), 2.42 (t, J=4.7 Hz, 2H, piperazine NCH2), 3.45 (t, J=4.9 Hz, 4H, piperazine N(CH2)2), 3.54 (s, 2H, CH2), 8.78 (s, 2H, pyrimidine H-4 & H-6), 9.15 (s, 1H, pyrimidine H-2);

Workup

  1. customthe reaction
  2. stirringthen stirred for 16 h
  3. concentrationConcentration
  4. customin vacuo and preparative tlc purification (EtOAc)

Sources & evidence

ORD record
ord-437bfc179a3e4385a3543f9da1740b65
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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