Dichloromethane → HCID 67282369, compound

HRID 913029Notes

Reaction equation

HRID 913029 reaction equation
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][NH:11][C:10]=1[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:23]([CH:27](OC)[OH:28])([F:26])([F:25])[F:24].ClCCl>O>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[C:13]([CH:27]([OH:28])[C:23]([F:26])([F:25])[F:24])=[CH:12][NH:11][C:10]=1[CH3:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 98922,2,2-Trifluoro-1-methoxyethanolHCID 11430Potassium CarbonateHCID 27264163-(BENZYLOXY)-2-METHYL-4(1H)-PYRIDINONE

Product 1

HCID 67282369HCID 67282369, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 3-benzyloxy-2-methyl-1H-pyridin-4-one (10.0 g, 46.4 mmol), potassium carbonate (19 g, 138 mmol), and CF3CH(OH)OCH3 (35 mL, 0.35 mol) in a 500 mL 3-necked round bottom flask equipped with a mechanical stirrer was heated to reflux for 6 days. The progress of the reaction was monitored by HPLC Method 3 (Example 24). Analysis of the HPLC data indicated that there was about 42% conversion. The reaction was stopped, and dichloromethane and deionized water were added. The organic fraction was collected, washed with brine, dried over Na2SO4, filtered and concentrated to dryness. Purification of the residue by column chromatography on silica (methanol/dichloromethane 2/100 to 5/100 v:v) afforded 3-benzyloxy-2-methyl-5-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one as a solid product (3.5 g, 24% yield, HPLC Method 3 (Example 24), RT=14.3 min). 1H NMR (DMSO-d6) 8 ppm: 11.68 (br s, 1H), 7.58 (s, 1H), 7.35, (m, 5H), 5.34 (q, J=7.3 Hz, 1H), 5.06 (m, 2H), 2.08 (s, 3H); MS-ESI (m/z) 313.7 [M+1]+, 206.1, 91.1 (100%).

Workup

  1. customequipped with a mechanical stirrer
  2. temperaturewas heated
  3. temperatureto reflux for 6 days
  4. additionwere added
  5. customThe organic fraction was collected
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customPurification of the residue by column chromatography on silica (methanol/dichloromethane 2/100 to 5/100 v:v)

Sources & evidence

ORD record
ord-205ab1b1ff904283a7960ee3f2f451c1
Source dataset
uspto-grants-2011_09
Patent number
US08026261B2

Reaction notes

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