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

HRID 1516695Notes

Reaction equation

HRID 1516695 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]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=3)=[C:25]([CH:39]([CH3:41])[CH3:40])[CH:24]=[C:23]3[C:18]=2[C:19](=[O:44])[CH2:20][C:21]([CH3:43])([CH3:42])[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:33]=[CH:32][C:31]([C:34]([F:35])([F:37])[F:36])=[CH:30][CH:29]=3)=[C:25]([CH:39]([CH3:41])[CH3:40])[CH:24]=[C:23]3[C:18]=2[C:19](=[O:44])[CH2:20][C:21]([CH3:42])([CH3:43])[O:22]3)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 962WaterHCID 123472(Diethylamino)sulfur trifluorideHCID 69070570Rac-5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

Product 1

HCID 58003013Rac-5-(4-fluorophenyl)-6-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-oneYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

At −78° C., a solution of 51 μl (380 μmol) of diethylaminosulfur trifluoride in 1 ml of dichloromethane is slowly added dropwise to a solution of 170 mg (350 μmol) of rac-5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 21A) in 4.5 ml of dichloromethane, and the mixture is stirred at this temperature for 2.5 h. The mixture is then allowed to thaw slowly to −20° C. 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. Crystallization of the residue from cyclohexane/ethyl acetate (10:1) gives 77 mg of the target product. Column chromatography of the concentrated mother liquor on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1) gives a further 60 mg of the target compound.

Workup

  1. customthaw slowly to −20° C
  2. extractionthe mixture is extracted twice with ethyl acetate
  3. dry with materialThe combined organic phases are dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customCrystallization of the residue from cyclohexane/ethyl acetate (10:1)

Sources & evidence

ORD record
ord-dbdd485fd76849a4a89d8cd52ceacd65
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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