Di-tert-butyl azodicarboxylate → (S)-3-methoxy-1-(1-methylpyrrolidin-3-yl)-4-nitro-1H-pyrazole

HRID 928216Notes

Reaction equation

HRID 928216 reaction equation
[CH3:1][O:2][C:3]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][NH:5][N:4]=1.[CH3:11][N:12]1[CH2:16][CH2:15][C@@H:14]([OH:17])[CH2:13]1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1.CCOC(C)=O>[NH3:4].[CH3:15][CH2:14][O:17][C:3]([CH3:7])=[O:2].[CH3:1][O:2][C:3]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][N:5]([C@H:14]2[CH2:15][CH2:16][N:12]([CH3:11])[CH2:13]2)[N:4]=1

Participants

7

Reactant 3

HCID 97268Di-tert-butyl azodicarboxylateHCID 69513321-Methyl-3-pyrrolidinol, (-)-HCID 178494320HCID 178494320, compound

Product 2

HCID 18464838Ammonia ethyl acetateYield 10%HCID 118073571(S)-3-methoxy-1-(1-methylpyrrolidin-3-yl)-4-nitro-1H-pyrazoleYield 150.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 3-methoxy-4-nitro-1H-pyrazole (2.00 g, 14.0 mmol, 1.00 eq), (R)-1-methyl-pyrrolidin-3-ol (1.56 g, 15.4 mmol, 1.10 eq), and polystyrene bound triphenylphosphine (6.53 g, 19.6 mmol, 1.40 eq, 3 mmol/gram) in THF (140 mL) was added a solution of di-tert-butyl azodicarboxylate (4.51 g, 19.6 mmol, 1.40 eq) in THF (25 mL) in a drop-wise manner over 5 min. The reaction mixture was allowed to stir for 18 hr. The reaction mixture was then diluted with EtOAc (100 mL), filtered and the filtrate concentrated. The crude reaction mixture was purified via flash chromatography on silica gel eluting with a gradient of 50-100% EtOAc in heptane then to 10% 7 N methanolic ammonia/EtOAc to give the title compound (2.39 g, 80% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.69 (s, 1H), 4.84-4.72 (m, 1H), 3.94 (s, 3H), 2.86-2.75 (m, 2H), 2.72 (dd, J=7.0, 10.0 Hz, 1H), 2.40 (dt, J=6.2, 8.4 Hz, 1H), 2.36-2.29 (m, 1H), 2.28 (s, 3H), 2.16-2.06 (m, 1H). m/z (APCI+) for C9H15N4O3 227.2 (M+H)+.

Workup

  1. filtrationfiltered
  2. concentrationthe filtrate concentrated
  3. customThe crude reaction mixture
  4. customwas purified via flash chromatography on silica gel eluting with a gradient of 50-100% EtOAc in heptane

Sources & evidence

ORD record
ord-f931de4d914445848767c7c3d305e090
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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