2,2,2-Trifluoroethanol → HCID 67979519, compound

HRID 1770908Notes

Reaction equation

HRID 1770908 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].[H-].[Na+].CS(O[CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([Br:21])[CH:20]=1)(=O)=O>C1COCC1.CN(C=O)C>[Br:21][C:19]1[CH:18]=[N:17][CH:16]=[C:15]([CH2:14][O:4][CH2:3][C:2]([F:6])([F:5])[F:1])[CH:20]=1

Participants

6

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 57885697HCID 57885697, compound

Product 1

HCID 67979519HCID 67979519, compoundYield 20.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2,2,2-Trifluoroethanol (0.434 g, 4.34 mmol) was added to a suspension of NaH (0.198 g, 4.96 mmol) in THF (10 mL). When gas evolution had ceased, a solution of (5-bromopyridin-3-yl)methyl methanesulfonate (see WO2007/076247; 1.10 g, 4.13 mmol) in DMF was added. The resulting mixture was stirred for 2 h at r.t. and then the volatile solvent was evaporated. The remaining solution was diluted with water and extracted with EtOAc (3×30 mL). The combined extracts were dried over MgSO4 and concentrated. The residue was purified by flash chromatography on silica using gradient elution with EtOAc in heptane to give 227 mg of the title compound (20% yield). 1H NMR (500 MHz, CDCl3) δ ppm 3.92 (q, 2H), 4.70 (s, 2H), 7.87 (m, 1H), 8.50 (m, 1H), 8.66 (d, 1H); MS (EI) m/z 269 M+.

Workup

  1. customthe volatile solvent was evaporated
  2. additionThe remaining solution was diluted with water
  3. extractionextracted with EtOAc (3×30 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica using gradient elution with EtOAc in heptane

Sources & evidence

ORD record
ord-0fd4109888f44acdbea9168596c8a7d7
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

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