tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(oxetan-3-YL)piperazine-1-carboxylate

HRID 1922678Notes

Reaction equation

HRID 1922678 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:14]1[CH2:17][C:16](=O)[CH2:15]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:16]2[CH2:17][O:14][CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-Oxetanone

Product 1

HCID 59605443Tert-butyl 4-(oxetan-3-YL)piperazine-1-carboxylateYield 59.5%

Procedure

A solution of piperazine-1-carboxylic acid tert-butyl ester (1.56 g, 8.38 mmol) and oxetan-3-one (500 mg, 6.94 mmol) DCE (60 mL) was stirred at ambient temperature for 90 min. Sodium triacetoxyborohydride (2.34 g, 11.04 mmol) was added and the mixture stirred for 17 h, then loaded onto an Isolute® SCX-2 cartridge (25 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM: MeOH; 100:0 to 99:1 to 98:2) to afford 4-Oxetan-3-ylpiperazine-1-carboxylic acid tert-butyl ester as a white solid (1.0 g, 59%). 1H NMR (CDCl3, 400 MHz) δ 4.69-4.58 (m, 4H); 3.51-3.44 (m, 5H); 2.27 (m, 4H) and 1.46 (s, 9H).

Workup

  1. washThe cartridge was then washed with methanol
  2. washthe desired product was subsequently eluted
  3. customThe product was collected
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM: MeOH; 100:0 to 99:1 to 98:2)

Sources & evidence

ORD record
ord-1b6ec6c94dd54cb0a3ad041bc581067e
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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