Sodium Iodide → (S)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-p-tolylsulfanylmethylpentan-2-ol

HRID 854163Notes

Reaction equation

HRID 854163 reaction equation
[F:1][C:2]([F:29])([F:28])[C@@:3]([CH2:18][S@:19]([C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)=O)([OH:17])[CH2:4][C:5]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[O:15][CH3:16])([CH3:7])[CH3:6].[I-].[Na+].FC(F)(F)C(OC(=O)C(F)(F)F)=O>CC(C)=O>[F:29][C:2]([F:1])([F:28])[C@@:3]([CH2:18][S:19][C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)([OH:17])[CH2:4][C:5]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[O:15][CH3:16])([CH3:7])[CH3:6]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 9845Trifluoroacetic anhydrideHCID 16115562(S)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol

Product 1

HCID 16115564(S)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-p-tolylsulfanylmethylpentan-2-olYield 100.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

To a suspension of (S)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (44.2 g, 102 mmol) and sodium iodide (46.0 g, 307 mmol) in 600 mL of anhydrous acetone at −40° C. was added a solution of trifluoroacetic acid anhydride (72.2 mL, 511 mmol) in 200 mL of anhydrous acetone via an addition funnel dropwise over 30 minutes. A greenish brown mixture was formed instantaneously. After 15 minutes, the reaction mixture was quenched with saturated aqueous sodium sulfite (Na2SO3) solution and neutralized with saturated aqueous sodium carbonate (Na2CO3) solution. The brown color disappeared and the crude product was concentrated to remove most of the acetone solvent. The resulting material was diluted with water and extracted three times with ether (one 600 mL portion and two 400 mL portions). The combined organic phases were washed with brine, dried over magnesium sulfate (MgSO4), filtered, and concentrated in vacuo to afford (S)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-p-tolylsulfanylmethylpentan-2-ol as an orange oil (42.7 g, 100%).

Workup

  1. customA greenish brown mixture was formed instantaneously
  2. customthe reaction mixture was quenched with saturated aqueous sodium sulfite (Na2SO3) solution
  3. concentrationthe crude product was concentrated
  4. customto remove most of the acetone solvent
  5. additionThe resulting material was diluted with water
  6. extractionextracted three times with ether (one 600 mL portion and two 400 mL portions)
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried over magnesium sulfate (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7955a75c5a2c4d0c83019c7ecdeb86a1
Source dataset
uspto-grants-2007_08
Patent number
US07256300B2

Reaction notes

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