Sodium Iodide → (S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-p-tolylsulfanylmethylpentan-2-ol

HRID 854169Notes

Reaction equation

HRID 854169 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([CH3:30])([CH3:29])[CH2:12][C@:13]([CH2:19][S@:20]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)=O)([OH:18])[C:14]([F:17])([F:16])[F:15])[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1.[I-].[Na+].FC(F)(F)C(OC(=O)C(F)(F)F)=O>CC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([CH3:30])([CH3:29])[CH2:12][C@:13]([CH2:19][S:20][C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)([OH:18])[C:14]([F:17])([F:15])[F:16])[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 9845Trifluoroacetic anhydrideHCID 69416142(S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol

Product 1

HCID 69419561(S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-p-tolylsulfanylmethylpentan-2-olYield 99.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

To a suspension of (S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (1.49 g, 3.23 mmol) and sodium iodide (1.45 g, 9.70 mmol) in 25 mL of anhydrous acetone at −40° C. was added a solution of trifluoroacetic acid anhydride (2.28 mL, 16.2 mmol) in 5 mL of anhydrous acetone via a syringe dropwise over 5 minutes. A greenish brown mixture was formed instantaneously. After 15 minutes, the reaction mixture was quenched with saturated aqueous sodium sulfite solution and neutralized with saturated aqueous sodium carbonate solution. The brown color disappeared and the crude was concentrated in vacuo to remove most of the acetone solvent. The resulting material was diluted with 50 mL of water and extracted with three 100 mL portions of ether. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford (S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-p-tolylsulfanylmethylpentan-2-ol as a yellow oil (1.43 g, 99%).

Workup

  1. customA greenish brown mixture was formed instantaneously
  2. customthe reaction mixture was quenched with saturated aqueous sodium sulfite solution
  3. concentrationthe crude was concentrated in vacuo
  4. customto remove most of the acetone solvent
  5. additionThe resulting material was diluted with 50 mL of water
  6. extractionextracted with three 100 mL portions of ether
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3d5cfdae34194a0babc69f2770548c39
Source dataset
uspto-grants-2007_08
Patent number
US07256300B2

Reaction notes

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