Hydrochloric Acid → 2-(4-Trifluoromethyl-phenyl)-2-aza-spiro[4.5]decane-1,8-dione

HRID 2092667Notes

Reaction equation

HRID 2092667 reaction equation
[O:1]1[C:5]2([CH2:15][CH2:14][C:8]3([CH2:12][CH2:11][NH:10][C:9]3=[O:13])[CH2:7][CH2:6]2)OCC1.I[C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1.CNCCNC.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl>CN(C=O)C>[F:24][C:23]([F:26])([F:25])[C:20]1[CH:21]=[CH:22][C:17]([N:10]2[CH2:11][CH2:12][C:8]3([CH2:7][CH2:6][C:5](=[O:1])[CH2:15][CH2:14]3)[C:9]2=[O:13])=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 582301081,4-Dioxa-10-azadispiro[4.2.4.2]tetradecan-9-one

Product 1

HCID 582301722-(4-Trifluoromethyl-phenyl)-2-aza-spiro[4.5]decane-1,8-dioneYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

1,4-Dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one (60 mg, obtained in example 121, step 3) was dissolved in DMF (5 mL) at r.t. Then, 4-iodobenzotrifluoride (155 mg, [CAS Reg. No. 455-13-0]), N,N′-dimethylethylenediamine (sym) (50 mg), Cuprous iodide (81 mg) and K3PO4 (181 mg) were added to the reaction mixture. The mixture was heated at 70° C. for 16 hours and at reflux for 2 hours. The reaction mixture was cooled, poured into ice/water and HCl (2M, 50 mL) was added to the mixture. Stirring was continued for 1 hour at room temperature. The mixture was then extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a colorless solid (51 mg, 58%). MS (m/e): 312.3 [MH+].

Workup

  1. temperatureat reflux for 2 hours
  2. temperatureThe reaction mixture was cooled
  3. additionwas added to the mixture
  4. extractionThe mixture was then extracted two times with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-9d607557de9e4cb78f711e41420dd37e
Source dataset
uspto-grants-2013_05
Patent number
US08440710B2

Reaction notes

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