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

HRID 1516718Notes

Reaction equation

HRID 1516718 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]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=3)=[C:19]([CH:33]([CH3:35])[CH3:34])[CH:18]=[C:17]3[C:9]=2[C:10](=[O:36])[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:43])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:43])[C:22]3[CH:23]=[CH:24][C:25]([C:28]([F:29])([F:31])[F:30])=[CH:26][CH:27]=3)=[C:19]([CH:33]([CH3:34])[CH3:35])[CH:18]=[C:17]3[C:9]=2[C:10](=[O:36])[CH2:11][C:12]2([O:16]3)[CH2:13][CH2:14][CH2:15]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 123472(Diethylamino)sulfur trifluorideHCID 580030305-(4-Fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Product 1

HCID 580030465-(4-Fluorophenyl)-6-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

Under argon, 180 mg (0.32 mmol) of 5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]-methyl}-7-isopropylspiro[chromen-2,1′-cyclobutan]-4(3H)-one (Example 52A) are dissolved in 3.2 ml of toluene, 52 μl (0.39 mmol) of diethylaminosulfur trifluoride are slowly added at −78° C. and the mixture is stirred at −78° C. for 1 h. The temperature is then slowly increased to −60° C. After 2 h, water is 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, dried over sodium sulfate, filtered and concentrated. The crude product is purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 12:1). This gives 107 mg (66% of theory) of the title compound.

Workup

  1. temperatureThe temperature is then slowly increased to −60° C
  2. waitAfter 2 h
  3. extractionthe mixture is extracted twice with ethyl acetate
  4. washThe combined organic phases are washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 12:1)

Sources & evidence

ORD record
ord-9e4176d568e849d0b79e12b8f70d85b8
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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