Trifluoroacetic acid → 4-(5-(2-Amino-5-fluoro-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol

HRID 1694138Notes

Reaction equation

HRID 1694138 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[CH:25]=[C:24]([C:26]3[C:27]([NH2:33])=[N:28][CH:29]=[C:30]([F:32])[CH:31]=3)[O:23][N:22]=2)=[CH:18][CH:17]=1)C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>>[NH2:33][C:27]1[C:26]([C:24]2[O:23][N:22]=[C:21]([CH2:20][C:19]3[CH:34]=[CH:35][C:16]([OH:15])=[CH:17][CH:18]=3)[CH:25]=2)=[CH:31][C:30]([F:32])=[CH:29][N:28]=1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7520ThioanisoleHCID 516892Sodium BicarbonateHCID 592554543-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-5-fluoro-pyridin-2-ylamine

Product 1

HCID 592555204-(5-(2-Amino-5-fluoro-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenolYield 98%

Procedure

To a trifluoroacetic acid (5 mL) solution of 3-(3-(4-benzyloxy-benzyl)-isoxazol-5-yl)-5-fluoro-pyridin-2-ylamine (180 mg, 0.48 mmol) described in Example 173 was added thioanisole (225 μL, 1.92 mmol), which was stirred for 6 hours at room temperature. A saturated sodium hydrogencarbonate aqueous solution was added to this reaction solution 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 (heptane:ethyl acetate=1:2 ethyl acetate) to obtain the title compound (134.0 mg, 98%).

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 (heptane:ethyl acetate=1:2 ethyl acetate)

Sources & evidence

ORD record
ord-3c2fa9e98b9d49b9b96f9d46b825a133
Source dataset
uspto-grants-2012_04
Patent number
US08158657B2

Reaction notes

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