2,2,2-Trifluoroethanol → HCID 178467556, compound

HRID 78515Notes

Reaction equation

HRID 78515 reaction equation
[C:1]([C:4]1[S:8]/[C:7](=[N:9]\[C:10](=[O:19])[C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=2F)/[N:6]([CH2:20][C@H:21]2[CH2:25][CH2:24][CH2:23][O:22]2)[C:5]=1[CH3:26])(=[O:3])[CH3:2].[F:27][C:28]([F:32])([F:31])[CH2:29][OH:30].CC(C)([O-])C.[K+]>O1CCCC1.O>[C:1]([C:4]1[S:8]/[C:7](=[N:9]\[C:10](=[O:19])[C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=2[O:30][CH2:29][C:28]([F:32])([F:31])[F:27])/[N:6]([CH2:20][C@H:21]2[CH2:25][CH2:24][CH2:23][O:22]2)[C:5]=1[CH3:26])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 23665647Potassium tert-butoxideHCID 178467554HCID 178467554, compound

Product 1

HCID 178467556HCID 178467556, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To the solution of the product from Example 280A (360 mg, 0.91 mmol) in tetrahydrofuran (4 mL) was added 2,2,2-trifluoroethanol (227 mg, 2.27 mmol) and a 1.0 M solution of potassium tert-butoxide in tetrahydrofuran (2.27 mL, 2.27 mmol). The reaction mixture was stirred at room temperature for 24 hours. The mixture was diluted with water, and extracted with ethyl acetate. The organic extract was dried (Na2SO4), filtered and concentrated. Purification by reverse phase HPLC afforded the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.64-1.75 (m, 1H) 1.90-2.00 (m, 2H) 2.10-2.20 (m, 1H) 2.51 (s, 3H) 2.80 (s, 3H) 3.73 (dd, J=15.9, 7.3 Hz, 1H) 3.88 (dd, J=15.3, 6.7 Hz, 1H) 4.07 (dd, J=13.7, 8.2 Hz, 1H) 4.33-4.41 (m, 1H) 4.47 (dd, J=16.8, 8.2 Hz, 2H) 4.62 (dd, J=13.7, 2.8 Hz, 1H) 7.03 (d, J=8.5 Hz, 1H) 7.39 (dd, J=8.5, 2.8 Hz, 1H) 8.02 (d, J=2.8 Hz, 1H); MS (ESI) m/z 477 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe organic extract
  3. dry with materialwas dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by reverse phase HPLC

Sources & evidence

ORD record
ord-1c8fa117448845129763ffc5264ab2a5
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Reaction notes

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