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

HRID 1516701Notes

Reaction equation

HRID 1516701 reaction equation
C(N(S(F)(F)[F:7])CC)C.[C:10]([C:14]1[CH:19]=[CH:18][C:17]([CH:20](O)[C:21]2[C:22]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[C:23]3[C:28](=[CH:29][C:30]=2[CH:31]([CH3:33])[CH3:32])[O:27][C:26]([CH3:35])([CH3:34])[CH2:25][C:24]3=[O:36])=[CH:16][CH:15]=1)([CH3:13])([CH3:12])[CH3:11].O>ClCCl>[C:10]([C:14]1[CH:19]=[CH:18][C:17]([CH:20]([F:7])[C:21]2[C:22]([C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)=[C:23]3[C:28](=[CH:29][C:30]=2[CH:31]([CH3:32])[CH3:33])[O:27][C:26]([CH3:35])([CH3:34])[CH2:25][C:24]3=[O:36])=[CH:16][CH:15]=1)([CH3:11])([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 962WaterHCID 123472(Diethylamino)sulfur trifluorideHCID 58002954Rac-6-[(4-tert-butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

Product 1

HCID 58003037Rac-6-[(4-tert-butylphenyl)(fluoro)methyl]-5-(4-fluorophenyl)-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 46 μl (350 μmol) of diethylaminosulfur trifluoride in 1 ml of dichloromethane is slowly added dropwise to a solution of 150 mg (320 μmol) of rac-6-[(4-tert-butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 27A) 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 −15° 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. Column chromatography of the residue on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 10:1→5:1) gives the target compound.

Workup

  1. customthaw slowly to −15° 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. customColumn chromatography of the residue on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 10:1→5:1) gives the target compound

Sources & evidence

ORD record
ord-a78c3731ee5f443b88e16a97693ead35
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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