Hydrochloric Acid → HCID 59621054, compound

HRID 1803825Notes

Reaction equation

HRID 1803825 reaction equation
C(OC([NH:8][C@@H:9]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][O:39]C2CCCCO2)=[CH:32][CH:31]=1)[C:10]([NH:12][C@@H:13]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)[C:14]([O:16][CH3:17])=[O:15])=[O:11])=O)(C)(C)C.Cl.[N-:47]=[N+:48]=[N-].[Na+].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([O-])(O)=O.[Na+]>O1CCOCC1.N1C=CC=CC=1.O>[N:8]([C@@H:9]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][OH:39])=[CH:32][CH:31]=1)[C:10]([NH:12][C@@H:13]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)[C:14]([O:16][CH3:17])=[O:15])=[O:11])=[N+:47]=[N-:48]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 33557Sodium AzideHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 70821832HCID 70821832, compound

Product 1

HCID 59621054HCID 59621054, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
23 °C

Procedure

To a stirring solution of the amide 147 (5.5 g, 8.6 mmol) in dioxane (20 mL) at 23° C. was added a solution of 4 M HCl in dioxane (172 mL). The mixture was stirred for 4 h and concentrated in vacuo to afford crude, clear, viscous pale-yellow oil. A slurry of NaN3 (839 mg, 12.9 mmol) in pyridine (13 mL) was then cooled to 0° C. and trifluoromethanesulfonic anhydride (2.17 mL, 12.9 mmol) was added dropwise before allowing the mixture to warm to 23° C. and stir for 3 h. A solution of the amine hydrochloride 148 (4.22 g, 8.6 mmol) in H2O (6 mL) was then added followed by CuSO4.5H2O (321 mg, 1.29 mmol). The combined mixture was allowed to stir at 23° C. overnight. An aqueous saturated solution of NaHCO3 was then added and the organic layer was extracted 3×EtOAc. The combined organic extracts were washed 1×10% CuSO4, 2×1 M HCl, 1×brine, and dried over MgSO4. Solvents were removed in vacuo and the crude residue purified by flash chromatgraphy on silica gel using hexanes/ethyl actetate on a Biotage purification system yielding the azide 149 as a pale yellow, viscous oil (800 mg, 20%).

Workup

  1. concentrationconcentrated in vacuo
  2. customto afford crude
  3. stirringstir for 3 h
  4. stirringto stir at 23° C. overnight
  5. extractionthe organic layer was extracted 3×EtOAc
  6. washThe combined organic extracts were washed 1×10% CuSO4, 2×1 M HCl, 1×brine
  7. dry with materialdried over MgSO4
  8. customSolvents were removed in vacuo
  9. customthe crude residue purified by flash chromatgraphy on silica gel
  10. customon a Biotage purification system

Sources & evidence

ORD record
ord-80663d0b0e0142c3982bcd76b5224ee1
Source dataset
uspto-grants-2013_01
Patent number
US08354092B2

Reaction notes

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