1,2-Dichloroethane → 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

HRID 1614990Notes

Reaction equation

HRID 1614990 reaction equation
FC(F)(F)C(O)=O.FC(F)(F)[CH2:10][CH2:11][CH2:12][C:13]([OH:15])=O.C(Cl)CCl.[CH2:22]([N:24](CC)CC)C.[O:29]1[CH:33]=[CH:32][CH:31]=[N:30]1>C(Cl)Cl.O>[N:24]1[CH:10]=[CH:11][CH:12]=[C:13]([O:15][C:31]2[CH2:32][CH2:33][O:29][N:30]=2)[CH:22]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 9254IsoxazoleHCID 27824465,5,5-trifluoropentanoic Acid

Product 1

HCID 668185323-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole III-57 was synthesized in two steps from compound III-53 starting with deprotection using analogous conditions to Example 11. The resulting trifluoroacetic acid salt (1.0 equiv) is then dissolved in methylene chloride (0.11 M with respect to isoxazole after which 5,5,5-trifluoropentanoic acid (1.5 equiv), EDC (1.5 equiv) and triethylamine (3.0 equiv) are added. The reaction is allowed to stir for 14 h at room temperature after which point the reaction was transferred to a separatory funnel with excess water and methylene chloride. The organic layer was washed with saturate sodium bicarbonate (2×), dried over magnesium sulfate, and concentrated to provide a white solid which was purified by flash silica gel chromatography (gradient of ethyl acetate/methanol). [M+H]+=373.7 m/z. Activity: C

Workup

  1. additionare added
  2. washThe organic layer was washed with saturate sodium bicarbonate (2×)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customto provide a white solid which
  6. customwas purified by flash silica gel chromatography (gradient of ethyl acetate/methanol)

Sources & evidence

ORD record
ord-0eaef6ca08bf4957828b68a10445de7f
Source dataset
uspto-grants-2014_07
Patent number
US08765735B2

Reaction notes

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