Methanesulfonic acid 1-(3-benzyloxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-yl)-2,2,2-trifluoro-ethyl ester → 3-Hydroxy-1-methyl-2-(2,2,2-trifluoroethyl)-4(1H)-pyridinone

HRID 913014Notes

Reaction equation

HRID 913014 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:11]([CH3:16])[C:10]=1[CH:17](OS(C)(=O)=O)[C:18]([F:21])([F:20])[F:19])C1C=CC=CC=1.[H][H]>C(O)C.[Pd]>[OH:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:11]([CH3:16])[C:10]=1[CH2:17][C:18]([F:21])([F:19])[F:20]

Participants

5

Reactant 2

HCID 86623501Methanesulfonic acid 1-(3-benzyloxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-yl)-2,2,2-trifluoro-ethyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 249445483-Hydroxy-1-methyl-2-(2,2,2-trifluoroethyl)-4(1H)-pyridinoneYield 9.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of methanesulfonic acid 1-(3-benzyloxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-yl)-2,2,2-trifluoro-ethyl ester (2.80 g, 7.15 mmol) and 10% Pd/C (0.56 g) in ethyl alcohol was subjected to hydrogenation in a Parr apparatus under 50 psi hydrogen pressure for 90 min. The mixture was filtered through a pad of CELITE™, and the filtrate was concentrated to dryness. The residue was purified by flash column chromatography on silica gel using a mixture of isopropyl alcohol and a conc. NH4OH solution (90/10, v/v) as eluant. Fractions rich in the product were pooled together and evaporated to dryness, thereby affording 3-hydroxy-1-methyl-2-(2,2,2-trifluoro-ethyl)-1H-pyridin-4-one (first crop: 143 mg, 9.7% yield, second crop: 240 mg, 16.2% yield). 1H NMR (90 MHz, CD3OD) δ (ppm): 7.66 (d, J=7.2 Hz, 1H), 6.41 (d, J=7.4 Hz, 1H), 3.89 (q, J=10.2 Hz, 1H) and 3.82 (s, 3H); MS-ESI (m/z): 208 [M+1]+, 188.2, 168.2. HPLC purity (peak area percent) of both fractions are about 98% at λ=254 nm, RT=3.75 min (HPLC method is described in Part A above).

Workup

  1. filtrationThe mixture was filtered through a pad of 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 isopropyl alcohol
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-6c374bf63c384fe3a68701585941733d
Source dataset
uspto-grants-2011_09
Patent number
US08026261B2

Reaction notes

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