Phenol → HCID 21913948, compound

HRID 1008029Notes

Reaction equation

HRID 1008029 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Cl[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[C:15]([NH:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:14]([CH3:34])=[C:13]([CH3:35])[N:12]=1.[O-]C1C=CC=CC=1.[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:35][C:13]1[C:14]([CH3:34])=[C:15]([NH:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:16]([N+:17]([O-:19])=[O:18])=[C:11]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:12]=1

Participants

7

Reactant 4

HCID 996PhenolHCID 24758Sodium hydrideHCID 4445035Phenolate SodiumHCID 21913714Tert-butyl 2-{2-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]ethoxy}ethylcarbamate

Product 1

HCID 21913948HCID 21913948, compoundYield 83.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Phenol (5.33 g, 56.63 mmol) was added in small portions over a period of 10 minutes to a chilled (0°) suspension of sodium hydride (2.39 g of 60%, 59.75 mmol) in anhydrous tetrahydrofuran (100 mL). After the addition was complete, the reaction was allowed to stir at 0° for 30 minutes. A solution tert-butyl 2-{2-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]ethoxy}ethylcarbamate (20.67 g, 53.16 mmol) in tetrahydrofuran (100 mL) was added over a period of 1 hour while maintaining the temperature at 0° C. The ice bath was removed and the reaction mixture was heated to reflux. At 46 and 52 hours additional fresh sodium phenoxide (11.3 mmol) was added. Refluxing was continued for 2 hours after the second addition. The reaction mixture was diluted with ethyl acetate (500 mL); washed sequentially with water (3×100 mL), 1N sodium hydroxide (2×100 mL), and brine; dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography (450 g of silica gel eluting with 1/1 hexanes/ethyl acetate) to provide 19.85 g of tert-butyl 2-{2-[(2,3-dimethyl-5-nitro-6-phenoxypyridin-4-yl)amino]ethoxy}ethylcarbamate.

Workup

  1. temperaturea chilled
  2. additionAfter the addition
  3. customThe ice bath was removed
  4. temperaturethe reaction mixture was heated to reflux
  5. temperatureRefluxing
  6. waitwas continued for 2 hours
  7. additionafter the second addition
  8. washwashed sequentially with water (3×100 mL), 1N sodium hydroxide (2×100 mL), and brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography (450 g of silica gel eluting with 1/1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-e3f6123cfd684c18810e6313985b69d6
Source dataset
uspto-grants-2004_09
Patent number
US06797718B2

Reaction notes

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