HCID 67281758, compound → HCID 67282524, compound

HRID 1187502Notes

Reaction equation

HRID 1187502 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[C:13]([CH2:16][C:17]([F:20])([F:19])[F:18])=[CH:12][N:11]([CH3:21])[C:10]=1[CH3:22])C1C=CC=CC=1.[H][H]>CO.[Pd]>[OH:8][C:9]1[C:14](=[O:15])[C:13]([CH2:16][C:17]([F:20])([F:18])[F:19])=[CH:12][N:11]([CH3:21])[C:10]=1[CH3:22]

Participants

5

Reactant 2

HCID 67281758HCID 67281758, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 67282524HCID 67282524, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

A clear solution of 3-benzyloxy-1,2-dimethyl-5-(2,2,2-trifluoro-ethyl)-1H-pyridin-4-one (1.1 g, 3.53 mmol) in methanol (32 mL) was debenzylated using Pd/C (10 wt. %, dry basis, on activated carbon, wet, Degussa type E101 NE/W, 0.17 g) as catalyst in a hydrogen atmosphere at a pressure of 50 psi for 30 min. The reaction mixture was diluted with methanol (30 mL), and sonicated for 10 min. A CELITE™ bed was prepared on a sintered glass, and washed with 6M HCl (100 mL), followed by water (7×50 mL) and then methanol (2×50 mL) under suction. The reaction mixture was filtered through the pre-treated CELITE™ bed. The volume of the filtrate was reduced to about 20 mL by evaporation under reduced pressure. HPLC analysis (HPLC Method 1, Example 24) of the filtrate indicated the presence of about 42% (peak percent area) of the starting material. Another 150 mg of Pd/C was added, and the mixture was subjected to the debenzylation reaction condition for a further 20 min, and worked up as described above. The catalyst was filtered off, and the filtrate was evaporated to dryness to afford 3-hydroxy-1,2-dimethyl-5-(2,2,2-trifluoro-ethyl)-1H-pyridin-4-one as a solid product (0.54 g, 69% yield, HPLC Method 1 (Example 24), RT=9.9 min, HPLC purity (peak percent area): 99.3% at λ=280 nm). 1H NMR (DMSO-d5) δ ppm: 7.70 (s, 1H), 3.65 (s, 3H), 3.39 (q, J=11.5 Hz, 2H), 2.26 (s, 3H). MS-ESI (m/z) 222.2 ([M+1]+, 100%), 202.2, 182.2.

Workup

  1. customfor 30 min
  2. customsonicated for 10 min
  3. customA CELITE™ bed was prepared on a sintered glass
  4. washwashed with 6M HCl (100 mL)
  5. filtrationThe reaction mixture was filtered through the pre-treated CELITE™ bed
  6. customThe volume of the filtrate was reduced to about 20 mL by evaporation under reduced pressure
  7. additionAnother 150 mg of Pd/C was added
  8. customthe mixture was subjected to the debenzylation reaction condition for a further 20 min
  9. filtrationThe catalyst was filtered off
  10. customthe filtrate was evaporated to dryness

Sources & evidence

ORD record
ord-4fa4b9fda53b4d5f9284fcd16e136e78
Source dataset
uspto-grants-2014_03
Patent number
US08673943B2

Reaction notes

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