2,2,2-Trifluoroethanol → HCID 90389281, compound

HRID 1526584Notes

Reaction equation

HRID 1526584 reaction equation
N(OC(C)(C)C)=O.[Cl:8][C:9]1[N:14]=[CH:13][C:12](N)=[CH:11][C:10]=1[CH3:16].[CH2:17]([OH:22])[C:18]([F:21])([F:20])[F:19].C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[K+].[K+]>>[Cl:8][C:9]1[C:10]([CH3:16])=[CH:11][C:12]([O:22][CH2:17][C:18]([F:21])([F:20])[F:19])=[CH:13][N:14]=1

Participants

6

Reactant 5

HCID 64092,2,2-TrifluoroethanolHCID 6422Trifluoroacetic acidHCID 10906Tert-Butyl nitriteHCID 11430Potassium CarbonateHCID 122956076-Chloro-5-methylpyridin-3-amine

Product 1

HCID 90389281HCID 90389281, compoundYield 41.2%

Procedure

Tert-butyl nitrite (1.60 g, 0.0156 mol, Sigma-Aldrich) was added drop wise to a stirred solution of 6-chloro-5-methylpyridine-3-amine (2.0 g, 0.0140 mol) in trifluoroethanol (10.05 g, 0.100 mol) and TFA (2.42 g, 0.0212 mol) at ambient temperature, followed by slow addition of potassium carbonate (4.40 g). The reaction mixture was stirred at ambient temperature for 1 h. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate (2×300 mL). The combined organic layer were washed with brine, dried over sodium sulfate and concentrated. The crude residue was purified by silica gel column chromatography, eluting with 5% ethyl acetate in petroleum ether to give 2-chloro-3-methyl-5-(2,2,2-trifluoroethoxy)pyridine (1.30 g, 41.13% yield) as a reddish oil. MS m/z=225.02 [M+H]+.

Workup

  1. additionThe reaction mixture was poured into ice-cold water
  2. extractionextracted with ethyl acetate (2×300 mL)
  3. washThe combined organic layer were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude residue was purified by silica gel column chromatography
  7. washeluting with 5% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-aa3e740899184de78c94e794042a8ae9
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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