Water → 5-(4-Fluorophenyl)-6-{fluoro[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

HRID 1516723Notes

Reaction equation

HRID 1516723 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([CH:21](O)[C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)=[C:19]([CH:34]([CH3:36])[CH3:35])[CH:18]=[C:17]3[C:9]=2[C:10](=[O:37])[CH2:11][C:12]2([O:16]3)[CH2:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C(N(S(F)(F)[F:44])CC)C.O>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:20]([CH:21]([F:44])[C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:31])([F:32])[F:30])=[CH:26][CH:27]=3)=[C:19]([CH:34]([CH3:36])[CH3:35])[CH:18]=[C:17]3[C:9]=2[C:10](=[O:37])[CH2:11][C:12]2([O:16]3)[CH2:15][CH2:14][CH2:13]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 123472(Diethylamino)sulfur trifluorideHCID 580029385-(4-Fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Product 1

HCID 580029745-(4-Fluorophenyl)-6-{fluoro[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

Under argon, 159 mg (0.31 mmol) of 5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]-methyl}-7-isopropylspiro[chromen-2,1′-cyclobutan]-4(3H)-one (Example 58A) are dissolved in 3.1 ml of toluene, 49 μl (0.37 mmol) of diethylaminosulfur trifluoride are slowly added at −78° C. and the mixture is stirred at −78° C. for 2 h. Water is then added, and the mixture is extracted twice with ethyl acetate. The combined organic phases are washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution, and dried over sodium sulfate, filtered and concentrated. The crude product is purified on a silica gel column (mobile phase:cyclohexane/ethyl acetate 15:1). This gives 118 mg (74% of theory) of the title compound.

Workup

  1. extractionthe mixture is extracted twice with ethyl acetate
  2. washThe combined organic phases are washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified on a silica gel column (mobile phase:cyclohexane/ethyl acetate 15:1)

Sources & evidence

ORD record
ord-bab78db1c2654baba31be4d9d988227f
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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