2,2,2-Trifluoroethanol → HCID 178441287, compound

HRID 76259Notes

Reaction equation

HRID 76259 reaction equation
[CH2:1]([C:5]1=[CH:6][N:7]([C:21]([CH3:24])([CH3:23])[CH3:22])[S:8]/[C:9]/1=[N:10]\[C:11](=[O:20])[C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1F)[CH2:2][CH2:3][CH3:4].[CH2:25]([OH:30])[C:26]([F:29])([F:28])[F:27].CC(C)([O-])C.[K+]>C1COCC1.O>[F:27][C:26]([F:29])([F:28])[C:25]([OH:20])=[O:30].[CH2:1]([C:5]1=[CH:6][N:7]([C:21]([CH3:24])([CH3:23])[CH3:22])[S:8]/[C:9]/1=[N:10]\[C:11](=[O:20])[C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[O:30][CH2:25][C:26]([F:29])([F:28])[F:27])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 23665647Potassium tert-butoxideHCID 178441283HCID 178441283, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 178441287HCID 178441287, compoundYield 56.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of the product from Example 47A (101 mg, 0.27 mmol), trifluoroethanol (33 mg, 0.32 mmol) and potassium tert-butoxide (2 M) (340 μL, 0.68 mmol) in THF (10 mL) was stirred at rt for 12 hrs. The mixture was diluted with water, and extracted with EtOAc. The organic extract was dried (Na2SO4), filtered and concentrated. The residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous trifluoroacetic acid over 8 minutes (10 minutes run time) at a flow rate of 40 mL/minute to afford 34 mg (28%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (t, J=7.36 Hz, 3 H) 1.37-1.48 (m, 2 H) 1.65-1.75 (m, 2 H) 1.68 (s, 9 H) 4.50 (q, J=8.59 Hz, 2 H) 7.05 (d, J=8.59 Hz, 1 H) 7.34 (dd, J=8.90, 2.76 Hz, 1 H) 7.97 (s, 1 H) 8.11 (d, J=2.76 Hz, 1 H); MS (DCI/NH4+) m/z 449 (M+H)+.

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. dry with materialwas dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size)

Sources & evidence

ORD record
ord-a4574d8b15a24988a3cba9ed43ebd7f1
Source dataset
uspto-grants-2014_09
Patent number
US08835475B2

Reaction notes

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