Ethanol → HCID 67282625, compound

HRID 913018Notes

Reaction equation

HRID 913018 reaction equation
C([O:8][C:9]1[C:10](=[O:26])[CH:11]=[C:12]([CH:16](OS(C)(=O)=O)[C:17]([F:20])([F:19])[F:18])[N:13]([CH3:15])[CH:14]=1)C1C=CC=CC=1.C(O)C>CO.[Pd]>[OH:8][C:9]1[C:10](=[O:26])[CH:11]=[C:12]([CH2:16][C:17]([F:18])([F:19])[F:20])[N:13]([CH3:15])[CH:14]=1

Participants

5

Reactant 2

HCID 702EthanolHCID 86623503HCID 86623503, compound

Product 1

HCID 67282625HCID 67282625, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

In a 500-mL reaction vessel was placed methanesulfonic acid 1-(5-benzyloxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-yl)-2,2,2-trifluoro-ethyl ester (1.80 g, 4.60 mmol), and ethanol (120 mL). The mixture was sonicated to give a clear solution. To the solution was added 1.80 g of Pd/C (10 wt. %, dry basis, on activated carbon, wet, Degussa type E101 NE/W). Hydrogenation was carried out under a hydrogen atmosphere set at a pressure of 50 psi. The reaction was completed within 90 min. The reaction mixture was diluted with methanol (120 mL), and the resulting mixture was sonicated for 10 min. The reaction mixture was then filtered through a short hydrochloric acid pre-treated CELITE™ bed. The filtrate was collected, and concentrated in vacuo to a volume of about 100 mL. To the resulting solution was added morpholine polymer-bound beads (1% cross-linked w/DVB, 200-400 mesh, 2.5-4.0 mmol N/g, 5.2 g), and the mixture was vortexed for 3 h. The morpholine beads were removed by filtration. Upon partial concentration in vacuo, a solid separated and the first crop of the title compound was obtained as the free base (0.74 g, 77% yield, HPLC Method 1 (Example 24); RT=8.2 min, HPLC purity (peak percent area): 98.7% at x=280 nm). 1H NMR (CD3OD) δ ppm: 7.55 (s, 1H), 6.52 (s, 1H), 3.77 (q, J=10 Hz, 2H), 3.78 (s, 3H); MS-ESI (m/z): 208.2 ([M+1]+, 100%), 188.2, 139.2.

Workup

  1. customIn a 500-mL reaction vessel
  2. customThe mixture was sonicated
  3. customto give a clear solution
  4. customthe resulting mixture was sonicated for 10 min
  5. filtrationThe reaction mixture was then filtered through a short hydrochloric acid pre-treated CELITE™ bed
  6. customThe filtrate was collected
  7. concentrationconcentrated in vacuo to a volume of about 100 mL
  8. additionTo the resulting solution was added morpholine polymer-bound beads (1% cross-linked w/DVB, 200-400 mesh, 2.5-4.0 mmol N/g, 5.2 g)
  9. waitthe mixture was vortexed for 3 h
  10. customThe morpholine beads were removed by filtration
  11. concentrationUpon partial concentration in vacuo
  12. customa solid separated

Sources & evidence

ORD record
ord-0248dcf918ac4f3dba66f7f6f63e83f3
Source dataset
uspto-grants-2011_09
Patent number
US08026261B2

Reaction notes

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