HCID 86623499, compound → HCID 25018650, compound

HRID 1187464Notes

Reaction equation

HRID 1187464 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH3:16])[N:11]([CH3:17])[C:10]=1[CH:18](OS(C)(=O)=O)[C:19]([F:22])([F:21])[F:20])C1C=CC=CC=1>CCO.CC(O)C.O.[Pd]>[OH:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH3:16])[N:11]([CH3:17])[C:10]=1[CH2:18][C:19]([F:22])([F:20])[F:21]

Participants

6

Reactant 1

HCID 86623499HCID 86623499, compound

Product 1

HCID 25018650HCID 25018650, compoundYield 53%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

To a solution of the product obtained in step 2 above (1.46 g, 3.60 mmol) in 100 mL of EtOH was added 10% wet Pd—C (330 mg), and the mixture was hydrogenated under a hydrogen atmosphere at 50 psi pressure for 2 hrs. The reaction mixture was filtered through CELITE™, and the filtrate was concentrated to dryness. The residue was purified by flash column chromatography on silica gel using a mixture of i-PrOH and a 28-30% conc. NH4OH solution (80/20, v/v) as eluant. The solid obtained was stirred in a mixture of i-PrOH (4 mL) and H2O (1 mL), then collected by suction filtration. Then, the solid was thoroughly washed with 4 mL of a mixture of i-PrOH and H2O (9/1, v/v). The solid was then dried overnight in a vacuum oven at 40° C. to afford the title product, 3-hydroxy-1,6-dimethyl-2-(2,2,2-trifluoro-ethyl)-1H-pyridin-4-one (420 mg, 53% yield) as light orange powder. HPLC purity (peak area percent) of this compound is 97.2% at λ=254 nm using HPLC Method 2 as described above. 1H NMR (400 MHz, MeOD-D4) δ: 6.39 (s, 1H), 3.96 (q, J=10.1 Hz, 2H), 3.69 (s, 3H, NCH3), 2.42 (s, 3H); MS m/z 222.2 [M+1]+, 202.4, 182.3, 153.3.

Workup

  1. filtrationThe reaction mixture was filtered through CELITE™
  2. concentrationthe filtrate was concentrated to dryness
  3. customThe residue was purified by flash column chromatography on silica gel using
  4. additiona mixture of i-PrOH
  5. customThe solid obtained
  6. filtrationcollected by suction filtration
  7. washThen, the solid was thoroughly washed with 4 mL of a mixture of i-PrOH and H2O (9/1
  8. customThe solid was then dried overnight in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-cc9e55109097443b9df8fc7ba52d21ef
Source dataset
uspto-grants-2014_03
Patent number
US08673943B2

Reaction notes

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