Water → HCID 59370511, compound

HRID 2046652Notes

Reaction equation

HRID 2046652 reaction equation
[F:1][C:2]1[C:9]([CH2:10]O)=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:12]([F:15])([F:14])[F:13])[CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.O>O1CCCC1>[F:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:12]([F:13])([F:14])[F:15])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59370515HCID 59370515, compound

Product 1

HCID 59370511HCID 59370511, compoundYield 17.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution (10 mL) of 4-fluoro-5-(hydroxymethyl)-2-(trifluoromethyl)benzonitrile (545 mg) and triethylamine (0.862 mL) in tetrahydrofuran was added dropwise methanesulfonyl chloride (0.289 mL) at 0° C. After the dropwise addition, the mixture was stirred at room temperature for 1.5 hr, water was added to the mixture and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL) and sodium borohydride (400 mg) was added thereto. The reaction mixture was stirred for 1.5 hr and methanol (2.5 mL) was added thereto. The mixture was stirred for 30 min, and saturated aqueous sodium hydrogencarbonate was added thereto. The mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate=15:1→1:1) to give the title compound as a yellow oil (yield: 89 mg).

Workup

  1. additionAfter the dropwise addition
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
  6. additionsodium borohydride (400 mg) was added
  7. stirringThe reaction mixture was stirred for 1.5 hr
  8. additionmethanol (2.5 mL) was added
  9. stirringThe mixture was stirred for 30 min
  10. additionsaturated aqueous sodium hydrogencarbonate was added
  11. extractionThe mixture was extracted with ethyl acetate
  12. dry with materialthe extract was dried over anhydrous magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate=15:1→1:1)

Sources & evidence

ORD record
ord-9314c92f64474c67be970b62d8bbe15a
Source dataset
uspto-grants-2013_11
Patent number
US08592452B2

Reaction notes

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