Sulfuric Acid → HCID 19366988, compound

HRID 12394Notes

Reaction equation

HRID 12394 reaction equation
OS(O)(=O)=O.[N-:6]=[N+]=[N-].[Na+].[F:10][C:11]([F:30])([F:29])[C:12]([N:14]1[CH2:19][CH2:18][C:17]2([C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21](=[O:28])[CH2:20]2)[CH2:16][CH2:15]1)=[O:13].C([O-])(O)=O.[Na+]>O.C(Cl)(Cl)Cl>[F:10][C:11]([F:30])([F:29])[C:12]([N:14]1[CH2:19][CH2:18][C:17]2([C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:6][C:21](=[O:28])[CH2:20]2)[CH2:16][CH2:15]1)=[O:13]

Participants

7

Reactant 4

HCID 1118Sulfuric Acid2×HCID 33557Sodium AzideHCID 516892Sodium BicarbonateHCID 193669921'-(2,2,2-trifluoroacetyl)spiro[indene-1,4'-piperidin]-3(2H)-one

Product 1

HCID 19366988HCID 19366988, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent3×

Procedure

Concentrated H2SO4 (1.1 mL) was added slowly to sodium azide (2.49 g, 38.3 mmol) in water (2.7 mL) and chloroform (15 mL) keeping the temperature between 0-5° C. After 10 min the cold bath was removed and the reaction was stirred for 3 h at rt. Na2SO4 was added to the solution to dry it and the resulting chloroform solution (containing HN3) was then decanted into a solution of 19a (4.55 g, 15.3 mmol) in chloroform (16 mL). Concentrated H2SO4 (4.1 mL) was added and the reaction was stirred for 30 min. at rt. The mixture was heated to 50° C. for 45 min. and then stirred at rt for 2 h. The reaction was poured into sat. NaHCO3 solution and extracted with CH2C12 (3×) and with EtOAc (2×). The combined organics were dried (MgSO4), filtered and evaporated to give the crude product. The crude product was purified by flash chromatography on Biotage using EtOAc/CH2C12 (50-80%) to give 19b as lightly colored foam (2.6 g, 54%). (M+H)+=313. 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (s, 1H); 7.29 (d, J=7.8 Hz, 1H); 7.24 (t, J=7.8 Hz, 1H); 7.10 (t, J=7.6 Hz, 1H); 6.83 (d, J=7.8 Hz, 1H); 4.44 (d, J=13.9 Hz, 1H); 3.92 (d, J=14.1 Hz, 1H); 3.48 (t, J=13.2 Hz, 1H); 3.18 (t, J=11.9 Hz, 1H); 2.77 (m, 2H); 2.00 (m, 2H); 1.85 (m, 2H).

Workup

  1. custombetween 0-5° C
  2. customAfter 10 min the cold bath was removed
  3. additionNa2SO4 was added to the solution
  4. customto dry it
  5. stirringthe reaction was stirred for 30 min. at rt
  6. temperatureThe mixture was heated to 50° C. for 45 min.
  7. stirringstirred at rt for 2 h
  8. extractionextracted with CH2C12 (3×) and with EtOAc (2×)
  9. dry with materialThe combined organics were dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customto give the crude product
  13. customThe crude product was purified by flash chromatography on Biotage

Sources & evidence

ORD record
ord-e52b15a90a9149b6bff697b334b6add9
Source dataset
uspto-grants-2010_06
Patent number
US07728008B2

Reaction notes

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