Pyridine → 5-(4-Fluorophenyl)-7-isopropyl-6-[4-(trifluoromethoxy)benzoyl]spiro[chromen-2,1'-cyclobutan]-4(3H)-one

HRID 1516724Notes

Reaction equation

HRID 1516724 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O.ClCCl.N1C=CC=CC=1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[C:51]([CH:52]([OH:64])[C:53]3[CH:58]=[CH:57][C:56]([O:59][C:60]([F:63])([F:62])[F:61])=[CH:55][CH:54]=3)=[C:50]([CH:65]([CH3:67])[CH3:66])[CH:49]=[C:48]3[C:40]=2[C:41](=[O:68])[CH2:42][C:43]2([O:47]3)[CH2:46][CH2:45][CH2:44]2)=[CH:35][CH:34]=1>C(OCC)(=O)C.[OH-].[Na+]>[F:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]2[C:51]([C:52](=[O:64])[C:53]3[CH:58]=[CH:57][C:56]([O:59][C:60]([F:62])([F:63])[F:61])=[CH:55][CH:54]=3)=[C:50]([CH:65]([CH3:66])[CH3:67])[CH:49]=[C:48]3[C:40]=2[C:41](=[O:68])[CH2:42][C:43]2([O:47]3)[CH2:46][CH2:45][CH2:44]2)=[CH:37][CH:38]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6344Dichloromethane2×HCID 159087TriacetoxyperiodinaneHCID 580029385-(4-Fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Product 1

HCID 580029845-(4-Fluorophenyl)-7-isopropyl-6-[4-(trifluoromethoxy)benzoyl]spiro[chromen-2,1'-cyclobutan]-4(3H)-one

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

68 mg (0.16 mmol) of 1,1-dihydro-1,1,1-triacetoxy-1,2-benziodoxol-3(1H)-one are dissolved in 0.6 ml of abs. dichloromethane and cooled to −30° C. 9 μl (0.11 mmol) of pyridine are added, followed by the dropwise addition of 55 mg (0.11 mmol) of 5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro-[chromen-2,1′-cyclobutan]-4(3H)-one (Example 58A), dissolved in 0.4 ml of abs. dichloromethane. The mixture is slowly warmed to 0° C. and stirred at this temperature for 6 h. The mixture is diluted with ethyl acetate, 5 ml of 1 N aqueous sodium hydroxide solution are added and the mixture is then extracted twice with ethyl acetate. The combined organic phases are washed once with 1 N hydrochloric acid and twice with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated. The crude product is dried under high vacuum and then reacted without further purification. This gives 54 mg (98% of theory) of the title compound.

Workup

  1. dissolutiondissolved in 0.4 ml of abs
  2. additionare added
  3. extractionthe mixture is then extracted twice with ethyl acetate
  4. washThe combined organic phases are washed once with 1 N hydrochloric acid and twice with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dry with materialThe crude product is dried under high vacuum
  9. customreacted without further purification

Sources & evidence

ORD record
ord-be58dda404564a5a95c6a56e664ed471
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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