Phenol → HCID 21913716, compound

HRID 1245908Notes

Reaction equation

HRID 1245908 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[C:15]([NH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][OH:26])[C:14]([CH3:27])=[C:13]([CH3:28])[N:12]=1>O1CCCC1>[O-:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:28][C:13]1[C:14]([CH3:27])=[C:15]([NH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][OH:26])[C:16]([N+:17]([O-:19])=[O:18])=[C:11]([O:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:12]=1

Participants

6

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 21913098HCID 21913098, compound

Product 2

HCID 119047PhenolateHCID 21913716HCID 21913716, compoundYield 138%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (6.63 g of 60%, 166 mmol) was added to chilled (0° C.) anhydrous tetrahydrofuran (200 mL) and the mixture was allowed to stir for 15 minutes. A solution of phenol (15.07 g, 160 mmol) in tetrahydrofuran (150 mL) was added dropwise over a period of 1 hour. A solution of 5-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]pentan-1-ol (31.723 g, 110 mmol) in tetrahydrofuran (150 mL) was added dropwise over a period of 30 minutes while maintaining the reaction temperature at 0° C. The reaction mixture was allowed to warm to ambient temperature and then it was heated at reflux overnight. Analysis by thin layer chromatography indicated that the reaction was 50–60% complete. An additional equivalent of phenoxide was prepared and added to the reaction mixture at ambient temperature; then the reaction mixture was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (300 mL); washed sequentially with water (2×50 mL), 5% sodium hydroxide (2×50 mL)) and 1N sodium hydroxide (2×50 mL); dried over magnesium sulfate and then concentrated under reduced pressure. The residue was divided into two portions and purified by column chromatography (450 g of silica gel eluting with 1:1 hexanes:ethyl acetate to 1:3 hexanes:ethyl acetate) to provide 38.13 g of 5-[(2,3-dimethyl-5-nitro-6-phenoxypyridin-4-yl)amino]pentan-1-ol.

Workup

  1. temperatureto warm to ambient temperature
  2. temperatureit was heated
  3. temperatureat reflux overnight
  4. additionadded to the reaction mixture at ambient temperature
  5. temperaturethen the reaction mixture was heated
  6. temperatureat reflux overnight
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in ethyl acetate (300 mL)
  9. washwashed sequentially with water (2×50 mL), 5% sodium hydroxide (2×50 mL)) and 1N sodium hydroxide (2×50 mL)
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. custompurified by column chromatography (450 g of silica gel eluting with 1:1 hexanes:ethyl acetate to 1:3 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-c7c5ca1de18f465abacc4bd28805c290
Source dataset
uspto-grants-2006_10
Patent number
US07125890B2

Reaction notes

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