N,N'-Dimethylethylenediamine → 10-[4-(2,2,2-Trifluoro-1-hydroxy-ethyl)-phenyl]-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one

HRID 2092674Notes

Reaction equation

HRID 2092674 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.[F:16][C:17]([F:28])([F:27])[CH:18]([C:20]1[CH:25]=[CH:24][C:23](I)=[CH:22][CH:21]=1)[OH:19].CNCCNC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[F:16][C:17]([F:27])([F:28])[CH:18]([C:20]1[CH:25]=[CH:24][C:23]([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:22][CH:21]=1)[OH:19]

Participants

6

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 582301081,4-Dioxa-10-azadispiro[4.2.4.2]tetradecan-9-oneHCID 594408652,2,2-Trifluoro-1-(4-iodophenyl)ethanol2×

Product 1

HCID 6658017410-[4-(2,2,2-Trifluoro-1-hydroxy-ethyl)-phenyl]-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-oneYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

1,4-Dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one (352 mg, obtained in example 133, step 3) was dissolved in DMF (22 mL) at r.t. Then, 2,2,2-trifluoro-1-(4-iodophenyl)ethanol (755 mg, [CAS Reg. No. 857521-44-9; for synthesis see: Beyer et al., PCT Int. Appl. (2005), WO 2005061497 A1], N,N′-dimethylethylenediamine (sym) (294 mg), cuprous iodide (476 mg) and K3PO4 (1.06 g) were added to the reaction mixture. The mixture was heated to 80° C. for 4.5 hours. The reaction mixture was cooled down to 30° C. and more 2,2,2-trifluoro-1-(4-iodophenyl)ethanol (252 mg) was added. The mixture was re-heated to 80° C. for 2 hours. The reaction mixture was cooled, poured into ice/water and 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 (415 mg, 62%). MS (m/e): 386.4 [MH+].

Workup

  1. customfor synthesis
  2. temperatureThe reaction mixture was cooled down to 30° C.
  3. temperatureThe mixture was re-heated to 80° C. for 2 hours
  4. temperatureThe reaction mixture was cooled
  5. extractionextracted two times with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-3749a4febd65408296e66cb81fd880de
Source dataset
uspto-grants-2013_05
Patent number
US08440710B2

Reaction notes

Loading…