Sodium Azide → 3-azido-2,3-dimethyl-6-(1-methyl-4-nitro-1H-pyrazol-5-yl)dihydro-2H-pyran-4(3H)-one

HRID 521880Notes

Reaction equation

HRID 521880 reaction equation
[CH3:1][C:2]1[CH:7]([CH3:8])[O:6][CH:5]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[CH2:4][C:3]=1[O:18][Si](CC)(CC)CC.[N-:26]=[N+:27]=[N-:28].[Na+].[N+]([O-])([O-])=O.[NH4+].[Ce]>CC#N>[N:26]([C:2]1([CH3:1])[C:3](=[O:18])[CH2:4][CH:5]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[O:6][CH:7]1[CH3:8])=[N+:27]=[N-:28]

Participants

5

Reactant 3

HCID 33557Sodium AzideHCID 57418452Ammonium cerium-nitrateHCID 867138275-(5,6-dimethyl-4-((triethylsilyl)oxy)-3,6-dihydro-2H-pyran-2-yl)-1-methyl-4-nitro-1H-pyrazole2×

Product 1

HCID 867138293-azido-2,3-dimethyl-6-(1-methyl-4-nitro-1H-pyrazol-5-yl)dihydro-2H-pyran-4(3H)-oneYield 46%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of 5-(5,6-dimethyl-4-((triethylsilyl)oxy)-3,6-dihydro-2H-pyran-2-yl)-1-methyl-4-nitro-1H-pyrazole (507 mg, 1.38 mmol, intermediate 85) in dry MeCN (3.5 mL) cooled to −20° C. was added sodium azide (404 mg, 6.22 mmol) followed by a solution of cerium ammonium nitrate (2.27 g, 4.15 mmol) in CH3CN (10.4 mL) dropwise. The reaction mixture was stirred at −20° C. for 1 hr, slowly warmed to 0° C. over 1 hr then quenched with water (20 mL) and extracted with EtOAc (20 mL). The organic layer was washed with water (10 mL) and brine (10 mL), separated, dried over Na2SO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 3-azido-2,3-dimethyl-6-(1-methyl-4-nitro-1H-pyrazol-5-yl)dihydro-2H-pyran-4(3H)-one as a white solid (187 mg, 46%). 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 5.78 (dd, J=12.3, 3.2 Hz, 1H), 4.21 (s, 3H), 3.73 (dd, J=12.3, 6.2 Hz, 1H), 3.13 (dd, J=14.6, 12.3 Hz, 1H), 2.73 (dd, J=14.6, 3.2 Hz, 1H), 1.44 (s, 3H), 1.41 (d, J=6.1 Hz, 3H).

Workup

  1. temperatureslowly warmed to 0° C. over 1 hr
  2. customthen quenched with water (20 mL)
  3. extractionextracted with EtOAc (20 mL)
  4. washThe organic layer was washed with water (10 mL) and brine (10 mL)
  5. customseparated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-4c9d58bb9c7f4153929adb1972217dc1
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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