Water → HCID 67288909, compound

HRID 511835Notes

Reaction equation

HRID 511835 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][OH:6].[F:9][C:10]1[C:11]([C:17]#[N:18])=[N:12][CH:13]=[C:14](F)[CH:15]=1.O>CN(C)P(=O)(N(C)C)N(C)C>[F:9][C:10]1[C:11]([C:17]#[N:18])=[N:12][CH:13]=[C:14]([O:6][CH2:5][C:4]([F:8])([F:7])[F:3])[CH:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 64092,2,2-Trifluoroethanol2×HCID 24758Sodium hydride2×HCID 27832532-Cyano-3,5-difluoropyridine

Product 1

HCID 67288909HCID 67288909, compoundYield 50.6%

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent2×

Procedure

60% sodium hydride (0.219 g, 5.71 mmol) was added to a solution of 2,2,2-trifluoroethanol (0.257 ml, 3.57 mmol) in N,N,N′,N′,N″,N″-hexamethylphosphoric triamide (6 ml) at 0 oC and stirred for 1 hour. Then 3,5-difluoropicolinonitrile (1.0 g, 7.1 mmol) in N,N,N′,N′,N″,N″-hexamethylphosphoric triamide (4 mL) was added to the reaction mixture and stirred at room temperature for 20 hours. Then 2,2,2-trifluoroethanol (0.257 ml, 3.57 mmol) and 60% sodium hydride (0.22 g, 5.7 mmol) were added to the reaction mixture and stirred at room temperature for 3 hours. After reaction, the mixture was poured into water, and the aqueous phase was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (6:1-4:1) to give 398 mg (25% yield) of the title compound as a oily solution:

Workup

  1. stirringstirred at room temperature for 20 hours
  2. stirringstirred at room temperature for 3 hours
  3. customAfter reaction
  4. extractionthe aqueous phase was extracted with ethyl acetate
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (6:1-4:1)

Sources & evidence

ORD record
ord-7195ee4a2f564613b4921fc9a6149811
Source dataset
uspto-grants-2015_08
Patent number
US09101616B2

Reaction notes

Loading…