Water → Rac-5-(4-fluorophenyl)-6-{fluoro[4-(trifluoromethoxy)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

HRID 1516698Notes

Reaction equation

HRID 1516698 reaction equation
C(N(S(F)(F)[F:7])CC)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:26]([CH:27](O)[C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=3)=[C:25]([CH:40]([CH3:42])[CH3:41])[CH:24]=[C:23]3[C:18]=2[C:19](=[O:45])[CH2:20][C:21]([CH3:44])([CH3:43])[O:22]3)=[CH:13][CH:12]=1.O>ClCCl>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:26]([CH:27]([F:7])[C:28]3[CH:29]=[CH:30][C:31]([O:34][C:35]([F:36])([F:38])[F:37])=[CH:32][CH:33]=3)=[C:25]([CH:40]([CH3:41])[CH3:42])[CH:24]=[C:23]3[C:18]=2[C:19](=[O:45])[CH2:20][C:21]([CH3:43])([CH3:44])[O:22]3)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 962WaterHCID 123472(Diethylamino)sulfur trifluorideHCID 58002959Rac-5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

Product 1

HCID 58003019Rac-5-(4-fluorophenyl)-6-{fluoro[4-(trifluoromethoxy)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

At −78° C., a solution of 45 μl (340 μmol) of diethylaminosulfur trifluoride in 1 ml of dichloromethane is slowly added dropwise to a solution of 157 mg (310 μmol) of rac-5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 24A) in 4 ml of dichloromethane, and the mixture is stirred at this temperature for 2.5 h. The mixture is then allowed to thaw slowly to −15° C. and stirred for a further 1.5 h. Water is then added, and the mixture is extracted twice with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated under reduced pressure. Column chromatography of the residue on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 10:1→15:1) gives the target compound.

Workup

  1. customthaw slowly to −15° C.
  2. stirringstirred for a further 1.5 h
  3. extractionthe mixture is extracted twice with ethyl acetate
  4. dry with materialThe combined organic phases are dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customColumn chromatography of the residue on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 10:1→15:1) gives the target compound

Sources & evidence

ORD record
ord-7980b7af19f2403f89a9569d4da0f010
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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