3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → 3-(4-Methyl-3-oxopiperazin-1-yl)azetidine-1-carboxylic acid tert-butyl ester

HRID 1945514Notes

Reaction equation

HRID 1945514 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][C:3]1=[O:8].[C:9]([O:13][C:14]([N:16]1[CH2:19][C:18](=O)[CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:9]([O:13][C:14]([N:16]1[CH2:19][CH:18]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[C:3](=[O:8])[CH2:4]2)[CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 43990421-Methylpiperazin-2-oneHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 596058423-(4-Methyl-3-oxopiperazin-1-yl)azetidine-1-carboxylic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 1-methylpiperazin-2-one (128 mg, 1.12 mmol), 3-oxoazetidine-1-carboxylic acid tert-butyl ester (231 mg, 1.35 mmol) and 4 Å powdered molecular sieves (150 mg) in DCE (4 mL) was stirred at room temperature for 1.5 h before the addition of sodium triacetoxyborohydride (475 mg, 2.24 mmol). The reaction mixture was filtered through celite, washing with DCM. The filtrate was concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%) affording 3-(4-Methyl-3-oxopiperazin-1-yl)azetidine-1-carboxylic acid tert-butyl ester as an oil (211 mg, 70%). 1H NMR (CDCl3, 300 MHz): δ 3.99-3.92 (m, 2 H); 3.81 (dd, J=8.8, 5.1 Hz, 2 H); 3.36 (t, J=5.5 Hz, 2 H); 3.20-3.14 (m, 1 H); 3.08 (t, J=5.5 Hz, 2 H); 2.97 (s, 3 H); 2.70-2.56 (m, 2 H); 1.44 (s, 9 H).

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washwashing with DCM
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%)

Sources & evidence

ORD record
ord-0927843139a844768baf4ded66dc7c57
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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