N,N'-Dimethylethylenediamine → 10-(4-Trifluoromethyl-phenyl)-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one

HRID 2368802Notes

Reaction equation

HRID 2368802 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)[O:4][CH2:3][CH2:2]1.Br[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+]>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([CH2:14][CH2:15][C:5]4([O:4][CH2:3][CH2:2][O:1]4)[CH2:6][CH2:7]3)[C:9]2=[O:13])=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 582301081,4-Dioxa-10-azadispiro[4.2.4.2]tetradecan-9-one

Product 1

HCID 5822999310-(4-Trifluoromethyl-phenyl)-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-oneYield 59.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

1,4-Dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one (4 g) was dissolved in DMF (189 ml) at RT under an argon atmosphere. Then, 1-bromo-4-(trifluoromethyl)benzene (6.39 g), N,N′-dimethylethylenediamine (sym) (3.34 g), cuprous iodide (5.41 g) and K3PO4 (7.13 g) were added and the mixture was heated at 100° C. for 12 hours. The reaction mixture was cooled to RT, filtered and saturated aqueous NH4Cl solution was added. The mixture was then extracted twice with AcOEt, the combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated off in vacuo. The crude product was purified by flash chromatography (silica gel, gradient of 0% to 25% of acetronitrile in CH2Cl2) to give the title compound as white crystalline solid (4 g). MS (m/e): 356.146 [MH+].

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. additionsaturated aqueous NH4Cl solution was added
  4. extractionThe mixture was then extracted twice with AcOEt
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated off in vacuo
  9. customThe crude product was purified by flash chromatography (silica gel, gradient of 0% to 25% of acetronitrile in CH2Cl2)

Sources & evidence

ORD record
ord-3bdca73057494d97a0d870ea72e4d129
Source dataset
uspto-grants-2014_04
Patent number
US08703807B2

Reaction notes

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