Trifluoroacetic acid → 4-[[3-(2-Amino-5-chloro-3-pyridinyl)-5-isoxazolyl]methyl]phenol

HRID 1691304Notes

Reaction equation

HRID 1691304 reaction equation
FC(F)(F)C(O)=O.C([O:15][C:16]1[CH:35]=[CH:34][C:19]([CH2:20][C:21]2[O:25][N:24]=[C:23]([C:26]3[C:27]([NH2:33])=[N:28][CH:29]=[C:30]([Cl:32])[CH:31]=3)[CH:22]=2)=[CH:18][CH:17]=1)C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>O>[NH2:33][C:27]1[C:26]([C:23]2[CH:22]=[C:21]([CH2:20][C:19]3[CH:34]=[CH:35][C:16]([OH:15])=[CH:17][CH:18]=3)[O:25][N:24]=2)=[CH:31][C:30]([Cl:32])=[CH:29][N:28]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7520ThioanisoleHCID 516892Sodium BicarbonateHCID 59255519HCID 59255519, compound

Product 1

HCID 592555114-[[3-(2-Amino-5-chloro-3-pyridinyl)-5-isoxazolyl]methyl]phenolYield 62.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a trifluoroacetic acid (6 mL) solution of 3-(5-(4-benzyloxy-benzyl)-isoxazol-3-yl)-5-chloro-pyridin-2-ylamine (304 mg, 0.776 mmol) described in Manufacturing Example 29-2-3 was added thioanisole (364 mL, 3.10 mmol) at 0° C., which was stirred for 3 hours at room temperature. To this reaction mixture were added sodium hydrogencarbonate and water at 0° C., which was extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=20:1) to obtain the title compound (146 mg, 62%).

Workup

  1. extractionwhich was extracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under a reduced pressure
  7. customthe residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=20:1)

Sources & evidence

ORD record
ord-a0c3f226385b442eae28d8ff40f441f4
Source dataset
uspto-grants-2012_04
Patent number
US08153662B2

Reaction notes

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