Phenol → Tert-butyl 4-[(6-methyl-3-nitro-2-phenoxypyridin-4-yl)amino]butylcarbamate

HRID 11351Notes

Reaction equation

HRID 11351 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][CH2:23][CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH:14]=[C:13]([CH3:33])[N:12]=1>O1CCCC1>[CH3:33][C:13]1[N:12]=[C:11]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:16]([N+:17]([O-:19])=[O:18])=[C:15]([NH:20][CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:29])[CH3:31])[CH:14]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 12109135Tert-butyl 4-[(2-chloro-6-methyl-3-nitropyridin-4-yl)amino]butylcarbamate

Product 1

HCID 21973809Tert-butyl 4-[(6-methyl-3-nitro-2-phenoxypyridin-4-yl)amino]butylcarbamateYield 64.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Phenol (9.45 g, 100 mmol) was added over a period of 10 minutes to a chilled (0° C.) suspension of sodium hydride (4.24 g of 60%, 106 mmol) in anhydrous tetrahydrofuran (100 mL). The reaction mixture was allowed to stir at 0° C. for 30 minutes. A solution of tert-butyl 4-[(2-chloro-6-methyl-3-nitropyridin-4-yl)amino]butylcarbamate (33.92 g, 94.5 mmol) in anhydrous tetrahydrofuran (250 mL) was added over a period of 50 minutes while maintaining the reaction mixture at 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred overnight before being concentrated under reduced pressure. The residue was dissolved in ethyl acetate (500 mL), washed with 1N sodium hydroxide (300 mL), dried over magnesium sulfate and then concentrated to dryness. The crude product was purified by column chromatography (400 g silica gel eluting with 7:3 hexanes:ethyl acetate to provide 25.4 g of tert-butyl 4-[(6-methyl-3-nitro-2-phenoxypyridin-4-yl)amino]butylcarbamate.

Workup

  1. temperaturea chilled
  2. temperaturewhile maintaining the reaction mixture at 0° C
  3. temperatureto warm to ambient temperature
  4. stirringstirred overnight
  5. concentrationbefore being concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in ethyl acetate (500 mL)
  7. washwashed with 1N sodium hydroxide (300 mL)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated to dryness
  10. customThe crude product was purified by column chromatography (400 g silica gel eluting with 7:3 hexanes

Sources & evidence

ORD record
ord-50ec6fbfd98d4be997fd1a0e11cd3c83
Source dataset
uspto-grants-2006_08
Patent number
US07098221B2

Reaction notes

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