ethyl N-ethoxycarbonyliminocarbamate → tert-butyl 3-(3-methoxy-4-nitro-1H-pyrazol-1-yl)azetidine-1-carboxylate

HRID 928212Notes

Reaction equation

HRID 928212 reaction equation
[CH3:1][O:2][C:3]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][NH:5][N:4]=1.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH:20](O)C1)=[O:17])([CH3:14])([CH3:13])[CH3:12].N(C(OCC)=O)=NC(OCC)=O>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][N:5]([CH:21]2[CH2:22][N:18]([C:16]([O:15][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:17])[CH2:20]2)[N:4]=1

Participants

6

Reactant 3

HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 44169391-Boc-3-pyrrolidinolHCID 178494320HCID 178494320, compound

Product 1

HCID 118073710tert-butyl 3-(3-methoxy-4-nitro-1H-pyrazol-1-yl)azetidine-1-carboxylateYield 72.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cooled (0° C.) suspension of 3-methoxy-4-nitro-1H-pyrazole (1.00 g, 6.99 mmol, 1.00 eq), tert-butyl-3-hydroxypyrrolidine-1-carboxylate (2.12 g, 12.2 mmol, 1.75 eq), and polystyrene bound triphenylphosphine (4.06 g, 12.2 mmol, 1.75 eq, 3 mmol/gram) in THF (45 mL) was added diethyl azodicarboxylate (2.42 mL, 13.0 mmol, 1.90 eq) in a drop-wise manner over 3 min. The reaction mixture was allowed to warm to ambient temperature and stirred for 15 hr. The reaction mixture was then diluted with EtOAc (60 mL), filtered and the filtrate concentrated. The crude reaction mixture was purified via flash chromatography on silica gel eluting with a gradient of 0-60% EtOAc in heptane to give the title compound (1.52 g, 72.9% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.12 (s, 1H) 4.87 (tt, J=5.6, 7.5 Hz, 1H) 4.40-4.28 (m, 4H) 4.09 (s, 3H) 1.48 (s, 9H). m/z (APCI+) for C7H11N4O3 198.9 (M−Boc+H)+.

Workup

  1. temperatureTo a cooled
  2. filtrationfiltered
  3. concentrationthe filtrate concentrated
  4. customThe crude reaction mixture
  5. customwas purified via flash chromatography on silica gel eluting with a gradient of 0-60% EtOAc in heptane

Sources & evidence

ORD record
ord-f37ea0bb011c4c07a11b3e80201942a0
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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