Sodium Bicarbonate → 2,2,2-Trifluoro-N-(1,2,3,4-tetrahydroisoquinolin-4-yl)acetamide

HRID 919620Notes

Reaction equation

HRID 919620 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]([NH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[N:8][CH:7]=1)=[O:4].C([O-])(O)=O.[Na+]>CC(O)=O.O.O=[Pt]=O>[F:17][C:2]([F:1])([F:16])[C:3]([NH:5][CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][NH:8][CH2:7]1)=[O:4]

Participants

6

Reactant 2

HCID 516892Sodium BicarbonateHCID 12120564HCID 12120564, compound

Product 1

HCID 121205692,2,2-Trifluoro-N-(1,2,3,4-tetrahydroisoquinolin-4-yl)acetamideYield 104.4%

Reagents, catalysts & solvents 3

HCID 345198Adams' catalystCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-(isoquinolin-4-yl)acetamide (1.0 g, 1.49 mmol) in AcOH (20 mL) was adde PtO2 (0.2 g) was added under nitrogen atmosphere. The reaction mixture placed under an atmosphere of hydrogen at rt for 10 h. The reaction mixture was filtered through a pad of celite, washed several times with MeOH. The filtrate was concentrated in vacuo to give a residue that was diluted with water, neutralized with NaHCO3, extracted with EtOAc (100 mL×3), the combined EtOAc layer was washed with water, dried over Na2SO4 and concentrated in vacuo to give a crude reaction mixture which was purified by column chromatography (silica gel, gradient MeOH in EtOAc) to give (0.380 g, 33%) of the titled intermediate. 1H NMR (DMSO-d6, 400 MHz): δ 9.72 (s, 1H), 7.24-7.07 (m, 4H), 4.98 (s, 1H), 3.89 (d, J=16.4 Hz, 1H), 3.82 (d, J=16.4 Hz, 1H), 3.10 (dd, J=4.8, 12.8 Hz, 1H), 2.88 (dd, J=6.8 Hz, 12.8 Hz, 1H), 2.50 (m, 1H). LCMS: M/z: (M+1):245

Workup

  1. additionwas added under nitrogen atmosphere
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washwashed several times with MeOH
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto give a residue that
  6. extractionextracted with EtOAc (100 mL×3)
  7. washthe combined EtOAc layer was washed with water
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customto give a crude
  11. customreaction mixture which
  12. customwas purified by column chromatography (silica gel, gradient MeOH in EtOAc)

Sources & evidence

ORD record
ord-6d21e7cb93dd4e028428830c32fde7aa
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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