Chloride → 6-(2-tert-butylphenoxy)-N-methyl-5-nitropyridin-2-amine

HRID 555415Notes

Reaction equation

HRID 555415 reaction equation
[CH3:1][NH2:2].[C:3]([C:7]1[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=1[O:9][C:10]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][CH:13]=[C:12](Cl)[N:11]=1)([CH3:6])([CH3:5])[CH3:4].[Cl-]>O1CCOCC1.O>[C:3]([C:7]1[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=1[O:9][C:10]1[N:11]=[C:12]([NH:2][CH3:1])[CH:13]=[CH:14][C:15]=1[N+:16]([O-:18])=[O:17])([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 3

HCID 312ChlorideHCID 6329Methylamine2×HCID 598574142-(2-Tert-butylphenoxy)-6-chloro-3-nitropyridine

Product 1

HCID 598573616-(2-tert-butylphenoxy)-N-methyl-5-nitropyridin-2-amineYield 61.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Methylamine (280 μL, 0.56 mmol) was added into a solution of 136b (157 mg, 0.51 mmol) in 1,4-dioxane at 0° C. (1 mL) over 1 h and the resulting reaction mixture was stirred at rt. After 72 h, 40% of the starting chloride remained by HPLC. Another 1.1 eq of methylamine was added at −10° C. over 30 min. The reaction was allowed to warm to rt, stir for 30 min and was then diluted with water (1 mL) and extracted with ethyl acetate (3×1 mL). The combined organic layer was washed with brine (1 mL), dried over sodium sulfate, and concentrated to give a yellow oil. The oil was purified by SiO2 chromatography (12 g) using a gradient of ethyl acetate in hexanes to afford 136c (94 mg, 61% yield) as a yellow oil; HPLC purity 100%, 3.76 min (Method A); [M+H]+=302.24.

Workup

  1. customthe resulting reaction mixture
  2. temperatureto warm to rt
  3. stirringstir for 30 min
  4. extractionextracted with ethyl acetate (3×1 mL)
  5. washThe combined organic layer was washed with brine (1 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto give a yellow oil
  9. customThe oil was purified by SiO2 chromatography (12 g)

Sources & evidence

ORD record
ord-f3c2cd49bc134bc883984deff0591eb2
Source dataset
uspto-grants-2011_11
Patent number
US08053450B2

Reaction notes

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