Nitrogen → HCID 89183088, compound

HRID 716178Notes

Reaction equation

HRID 716178 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][S:5][C:6]=1[N:7]1[CH2:12][CH2:11][CH2:10][C@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:8]1.OS(O)(=O)=O.N([O-])=O.[Na+].[N-:30]=[N+:31]=[N-].[Na+].N#N.C([O-])([O-])=O.[Na+].[Na+]>O.CC(C)=O>[N:1]([C:2]1[CH:3]=[N:4][S:5][C:6]=1[N:7]1[CH2:12][CH2:11][CH2:10][C@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:19])[CH3:18])[CH2:8]1)=[N+:30]=[N-:31]

Participants

9

Reactant 6

HCID 947NitrogenHCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 71007245HCID 71007245, compound

Product 1

HCID 89183088HCID 89183088, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent2×

Procedure

tert-butyl ((3S)-1-(4-azido-5-isothiazolyl)-3-piperidinyl) carbamate. A 25 mL, one neck round bottom flask was charged with tert-butyl ((3S)-1-(4-amino-5-isothiazolyl)-3-piperidinyl)carbamate (537 mg, 1.80 mmol), acetone (7 mL), water (7 mL) and a stirbar. The flask was immersed into a ice-water bath and stirred for 15 min. The solution was treated with 8 M H2SO4 (0.90 mL, 7.19 mmol), and stirred for 5 min. The homogenous solution was treated with NaNO2 (163 mg, 2.36 mmol) and stirred for 10 min. NaN3 (351 mg, 5.40 mmol) was added. The reaction was stirred cold for 30 min. The slurry was N2-pressure filtered cold through a 10 mL Bohdan glass frit fitted with a 0.22 μm PTFE, 25 mm syringe filter unit (Millipore, SLFG025NK). The filtrate was slowly added to a ice-cold solution of Na2CO3 (1.14 g, 10.79 mmol) in H2O (10 mL). The solids were washed with H2O (3×5 mL), and the washes were added to the Na2CO3 solution. The solids were dried in a vacuum oven (45° C., <1 mm Hg) for 20 min. The solids were dissolved in CHCl3, and treated with MgSO4. The resulting slurry was N2-pressure filtered through a 10 mL Bohdan glass frit fitted with a 0.22 μm PTFE, 25 mm syringe filter unit (Millipore, SLFG025NK). The solvent was removed in vacuo to afford tert-butyl ((3S)-1-(4-azido-5-isothiazolyl)-3-piperidinyl)carbamate (213 mg, 0.66 mmol, 37% yield). The material was used directly.

Workup

  1. customThe flask was immersed into a ice-water bath
  2. stirringstirred for 5 min
  3. stirringstirred for 10 min
  4. stirringThe reaction was stirred cold for 30 min
  5. filtrationfiltered cold through a 10 mL Bohdan glass frit
  6. customfitted with a 0.22 μm PTFE, 25 mm syringe
  7. filtrationfilter unit (Millipore, SLFG025NK)
  8. washThe solids were washed with H2O (3×5 mL)
  9. additionthe washes were added to the Na2CO3 solution
  10. customThe solids were dried in a vacuum oven (45° C., <1 mm Hg) for 20 min
  11. dissolutionThe solids were dissolved in CHCl3
  12. additiontreated with MgSO4
  13. filtrationfiltered through a 10 mL Bohdan glass frit
  14. customfitted with a 0.22 μm PTFE, 25 mm syringe
  15. filtrationfilter unit (Millipore, SLFG025NK)
  16. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-ec73e32adee24c5486b6df6fd1482a1b
Source dataset
uspto-grants-2015_11
Patent number
US09187486B2

Reaction notes

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