5-benzyloxy-2-difluoromethyl-1-methyl-1H-pyridin-4-one → 2-difluoromethyl-5-hydroxy-1-methyl-1H-pyridin-4-one

HRID 1187455

Reaction equation

HRID 1187455 reaction equation
C([O:8][C:9]1[C:10](=[O:19])[CH:11]=[C:12]([CH:16]([F:18])[F:17])[N:13]([CH3:15])[CH:14]=1)C1C=CC=CC=1>CO.[Pd]>[F:18][CH:16]([F:17])[C:12]1[N:13]([CH3:15])[CH:14]=[C:9]([OH:8])[C:10](=[O:19])[CH:11]=1

Participants

4

Reactant 1

HCID 672828605-benzyloxy-2-difluoromethyl-1-methyl-1H-pyridin-4-one

Product 1

HCID 250189082-difluoromethyl-5-hydroxy-1-methyl-1H-pyridin-4-oneYield 79.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

A mixture of 5-benzyloxy-2-difluoromethyl-1-methyl-1H-pyridin-4-one (1.90 g, 7.16 mmol) and 10% Pd/C (190 mg) in methanol (60 mL) was hydrogenated under a hydrogen atmosphere at 15 psi of pressure in a Parr apparatus for 25 min. The mixture was diluted with methanol (180 mL), sonicated for 15 min, and then filtered through a pad of CELITE™ (pre-treated with dilute HCl and washed to neutral with deionized water). The volume of the filtrate was reduced using a rotary evaporator until a solid precipitated out. The mixture was diluted with 2 mL of methanol and the solid was collected by suction filtration. The solid was thoroughly washed with ether, and then dried in a vacuum oven to afford the title product (1.00 g, 79% yield). HPLC purity (peak area percent) of the product is 99.2% at λ=288 nm using HPLC Method 1 as described above. 1H NMR (400 MHz, DMSO-D6) δ (ppm): 7.56 (s, 1H), 7.12 (t, J=52.7 Hz, 1H, CF2H), 6.47 (s, 1H), 3.70 (s, 3H, N—CH3); MS-ESI (m/z): 176.5 [M+1]+, 126.2; Anal. Calcd. for C7H7F2NO2: C, 48.01; H, 4.03; N, 8.00%. Found: C, 48.15; H, 4.14; N, 7.88%.

Workup

  1. customsonicated for 15 min
  2. filtrationfiltered through a pad of CELITE™ (pre-treated with dilute HCl and washed to neutral with deionized water)
  3. customa rotary evaporator until a solid
  4. customprecipitated out
  5. additionThe mixture was diluted with 2 mL of methanol
  6. filtrationthe solid was collected by suction filtration
  7. washThe solid was thoroughly washed with ether
  8. customdried in a vacuum oven

Sources & evidence

ORD record
ord-b215fd9ef5f8470dbb791257c79344f6
Source dataset
uspto-grants-2014_03
Patent number
US08673943B2

Linked notes

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