Hydrochloric Acid → 5-(5-(azidomethyl)-5-methyl-1,3-dioxan-2-yl)-1-methyl-4-nitro-1H-pyrazole

HRID 521876Notes

Reaction equation

HRID 521876 reaction equation
[CH2:1]([C:3]1([CH2:18]O)[CH2:8][O:7][CH:6]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[O:5][CH2:4]1)C.CCN(CC)CC.CS(Cl)(=O)=O.Cl.[N-:33]=[N+:34]=[N-:35].[Na+]>C(Cl)Cl.CN(C=O)C.O.CCOC(C)=O>[N:33]([CH2:18][C:3]1([CH3:1])[CH2:4][O:5][CH:6]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[O:7][CH2:8]1)=[N+:34]=[N-:35]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 86713820(5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methanol2×

Product 1

HCID 867138245-(5-(azidomethyl)-5-methyl-1,3-dioxan-2-yl)-1-methyl-4-nitro-1H-pyrazole

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (5-methyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methanol (trans isomer) (248 mg, 1.02 mmol, intermediate 66) in dry DCM at 0° C. (10 mL) was added Et3N (0.20 mL, 1.53 mmol) followed by methanesulfonyl chloride (0.10 mL, 1.22 mmol). The reaction mixture was slowly warmed to room temperature over 1.5 hr. The mixture was re-cooled to 0° C. and 1 M aqueous HCl (5 mL) and DCM (20 mL) were added. The organic layer was washed with saturated aqueous NaHCO3 (10 mL) and water (10 mL), separated, dried over Na2SO4 and concentrated under reduced pressure to yield a colourless oil. This oil was dissolved in DMF (20 mL) and sodium azide (400 mg, 6.12 mmol) was added. The reaction mixture was heated at 140° C. for 18 hr behind a blast shield. The reaction mixture was cooled to room temperature and diluted with water (20 mL) and EtOAc (50 mL). The organic layer was washed with water (3×20 mL), separated, dried over Na2SO4 and concentrated under reduced pressure to give 5-(5-(azidomethyl)-5-methyl-1,3-dioxan-2-yl)-1-methyl-4-nitro-1H-pyrazole as a colourless solid (300 mg, quantitative over two steps). 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 6.36 (s, 1H), 4.17 (s, 3H), 3.88 (s, 4H), 3.20 (s, 2H), 1.40 (s, 3H).

Workup

  1. temperatureThe mixture was re-cooled to 0° C.
  2. washThe organic layer was washed with saturated aqueous NaHCO3 (10 mL) and water (10 mL)
  3. customseparated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto yield a colourless oil
  7. temperatureThe reaction mixture was heated at 140° C. for 18 hr behind a blast shield
  8. temperatureThe reaction mixture was cooled to room temperature
  9. washThe organic layer was washed with water (3×20 mL)
  10. customseparated
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4339380ca72445adb1e5205c47a50e21
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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