Ammonia → 2-methoxy-N-(4-(2-methoxy-4-nitrophenoxy)pyridin-2-yl)acetamide

HRID 2069131Notes

Reaction equation

HRID 2069131 reaction equation
[CH3:1][O:2][C:3]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:4]=1[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH2:12])[CH:7]=1.CCN(C(C)C)C(C)C.[CH3:29][O:30][CH2:31][C:32](Cl)=[O:33].N>C1COCC1.CO>[CH3:29][O:30][CH2:31][C:32]([NH:12][C:8]1[CH:7]=[C:6]([O:5][C:4]2[CH:13]=[CH:14][C:15]([N+:17]([O-:19])=[O:18])=[CH:16][C:3]=2[O:2][CH3:1])[CH:11]=[CH:10][N:9]=1)=[O:33]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 585648114-(2-Methoxy-4-nitrophenoxy)pyridin-2-amine

Product 1

HCID 709217322-methoxy-N-(4-(2-methoxy-4-nitrophenoxy)pyridin-2-yl)acetamideYield 78.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-(2-methoxy-4-nitrophenoxy)pyridin-2-amine (233 mg, 0.892 mmol) in THF (5.0 mL) and DIPEA (775 μL, 6.12 mmol) at 0° C. was added 2-methoxyacetyl chloride (325 μL, 3.57 mmol) in a single portion. The reaction mixture was warmed to RT for 1 hr and then a solution of NH3 in MeOH (7M, 2.0 mL) was added. After 30 min at RT the mixture was evaporated in vacuo and the residue was partitioned between DCM (50 mL) and brine (40 mL). The organic phase was separated and dried (MgSO4) and was evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, 2% MeOH in DCM, isocratic elution) to afford 2-methoxy-N-(4-(2-methoxy-4-nitrophenoxy)pyridin-2-yl)acetamide as an orange oil (234 mg, 78%); Rt 1.89 min (Method 2); m/z 334 (M+H)+ (ES+).

Workup

  1. customAfter 30 min at RT the mixture was evaporated in vacuo
  2. customthe residue was partitioned between DCM (50 mL) and brine (40 mL)
  3. customThe organic phase was separated
  4. dry with materialdried (MgSO4)
  5. customwas evaporated in vacuo
  6. customThe residue was purified by flash column chromatography (SiO2, 40 g, 2% MeOH in DCM, isocratic elution)

Sources & evidence

ORD record
ord-8aef9103520540b48fcf855f0f345463
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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