Potassium Carbonate → 2-(2,2-difluoro-1-hydroxyethyl)-3-hydroxy-1-methylpyridin-4(1H)-one

HRID 1519053Notes

Reaction equation

HRID 1519053 reaction equation
[OH:1][C:2]1[C:7](=[O:8])[CH:6]=[CH:5][N:4]([CH3:9])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].C([O:18][CH:19](O)[CH:20]([F:22])[F:21])C>>[F:21][CH:20]([F:22])[CH:19]([C:3]1[N:4]([CH3:9])[CH:5]=[CH:6][C:7](=[O:8])[C:2]=1[OH:1])[OH:18]

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 27582461-Ethoxy-2,2-difluoroethanolHCID 30849364(1H)-Pyridinone, 3-hydroxy-1-methyl-

Product 1

HCID 668690812-(2,2-difluoro-1-hydroxyethyl)-3-hydroxy-1-methylpyridin-4(1H)-oneYield 25%

Conditions

Temperature
50 °C

Procedure

A sealed suspension of 3-hydroxy-1-methypyridin-4(1H)-one (1.00 g, 8.0 mmol) and potassium carbonate (0.11 g, 0.8 mmol) in 2.4 mL of difluoroacetaldehyde ethyl hemiacetal was heated to 50° C. for 18 h. The volatile components were evaporated under reduced pressure. The residue was dissolved in 3 mL of de-ionized water then cooled in an ice-water bath, and the pH was adjusted to 5-6 with a 1N HCl solution. The precipitate was collected by suction filtration and dried. Thus, the title compound Apo7078 was obtained (410 mg) as a white solid. Yield=25%; 1H NMR (400 MHz, CD3OD) δ (ppm): 7.62 (d, J=7.1 Hz, 1H), 6.41 (d, J=7.1 Hz, 1H), 6.30 (dt, 3J=55.8 Hz, 2J=5.1 Hz, 1H), 5.45 (dt, 2J=5.1 Hz, 3J=11.4 Hz, 1H), 3.96 (s, 3H); MS m/z 206 [M+1], 188 (100%).

Workup

  1. customThe volatile components were evaporated under reduced pressure
  2. dissolutionThe residue was dissolved in 3 mL of de-ionized water
  3. temperaturethen cooled in an ice-water bath
  4. filtrationThe precipitate was collected by suction filtration
  5. customdried

Sources & evidence

ORD record
ord-db5fd5c3a7e74adaa0df58dfba161856
Source dataset
uspto-grants-2015_07
Patent number
US09073865B2

Reaction notes

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