Potassium Carbonate → Tert-butyl 4-(4-amino-3-nitrophenoxy)picolinate

HRID 2070248Notes

Reaction equation

HRID 2070248 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][C:13]=1[N+:19]([O-:21])=[O:20].Cl[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH:24]=2)=[CH:14][C:13]=1[N+:19]([O-:21])=[O:20]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 37588824-Amino-3-NitrophenolHCID 11806045tert-Butyl 4-chloropicolinate

Product 1

HCID 22041090Tert-butyl 4-(4-amino-3-nitrophenoxy)picolinate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

Solid anhydrous white powdered KHMDS (2 eq) was suspended in a solution of dimethylformamide. Red crystalline 4-amino-3-nitrophenol (1 eq) was charged to the rapidly stirring solution under an inert atmosphere and the heterogeneous solution was allowed to stir for 2 hours. Then a dimethylformamide solution of tert-butyl 4-chloropyridine-2-carboxylate (1 eq) was added dropwise. Anhydrous powdered potassium carbonate (1.2 eq) was charged to the reaction as an acid scavenger. The purple colored viscous mixture was heated to 80° C. for 12-15 hours until when it was determined to be complete by HPLC. The reaction was evaporated under reduced pressure and diluted with excess ethyl acetate and water. An extraction of the aqueous layer was made with ethyl acetate. The organic layers were combined and washed 4 times with water followed by brine. The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude material was purified by flash silica gel chromatography using an eluent of 1:1 mixture of hexanes to ethyl acetate to give the desired product. MS: MH+=332.

Workup

  1. customThe reaction was evaporated under reduced pressure
  2. additiondiluted with excess ethyl acetate and water
  3. extractionAn extraction of the aqueous layer
  4. washwashed 4 times with water
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. customThe crude material was purified by flash silica gel chromatography
  8. additionan eluent of 1:1 mixture of hexanes to ethyl acetate

Sources & evidence

ORD record
ord-ea8b65479cd74d648c39745b5a6c46c2
Source dataset
uspto-grants-2012_10
Patent number
US08299108B2

Reaction notes

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