Trimethyl orthoformate → 1-Boc-3-(3-oxo-1-piperazinyl)azetidine

HRID 1922659Notes

Reaction equation

HRID 1922659 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][C:2]1=[O:7].[C:8]([O:12][C:13]([N:15]1[CH2:18][C:17](=O)[CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(OC)(OC)OC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>CC(O)=O.ClCCCl>[C:8]([O:12][C:13]([N:15]1[CH2:18][CH:17]([N:4]2[CH2:5][CH2:6][NH:1][C:2](=[O:7])[CH2:3]2)[CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

7

Reactant 4

HCID 9005Trimethyl orthoformateHCID 231360Piperazin-2-oneHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 2724942Triacetoxyborohydride

Product 1

HCID 596054391-Boc-3-(3-oxo-1-piperazinyl)azetidineYield 28%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent

Procedure

A mixture of piperazin-2-one (1.52 g, 15.1 mmol), 3-oxoazetidine-1-carboxylic acid tert-butyl ester (2.0 g, 11.6 mmol) and trimethyl orthoformate (12.8 mL, 12.4 g, 117 mmol) in AcOH (0.7 mL) and DCE (50 mL) was stirred for 5 h before the addition of triacetoxyborohydride (4.9 g, 23.2 mmol). The resulting mixture was stirred for 16 h then partitioned between DCM and H2O. The organic layer was dried (Na2SO4) and concentrated in vacuo. The resulting oil was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%) affording the title compound as a foam (827 mg, 28%). 1H NMR (CDCl3, 300 MHz): δ 6.24 (s, 1H); 3.97 (dd, J=8.9, 7.1 Hz, 2H); 3.82 (dd, J=5.2, 2.2 Hz, 2H); 3.40 (td, J=5.2, 2.2 Hz, 2H); 3.24-3.15 (m, 1H); 3.07 (s, 2H); 2.60 (t, J=5.4 Hz, 2H); 1.44 (s, 9H).

Workup

  1. customthen partitioned between DCM and H2O
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting oil was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)

Sources & evidence

ORD record
ord-2b5ab7baedc645739cbee2dbd01aaf10
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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