2,6-Dichloroisonicotinic acid → tert-Butyl 2,6-dichloropyridine-4-carboxylate

HRID 1372368Notes

Reaction equation

HRID 1372368 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[C:4]([Cl:11])[N:3]=1.C(NC(=NC(C)C)O[C:18]([CH3:21])([CH3:20])[CH3:19])(C)C>C1COCC1>[C:18]([O:9][C:8]([C:6]1[CH:5]=[C:4]([Cl:11])[N:3]=[C:2]([Cl:1])[CH:7]=1)=[O:10])([CH3:21])([CH3:20])[CH3:19]

Participants

4

Reactant 2

HCID 948302,6-Dichloroisonicotinic acidHCID 110417822-tert-Butyl-1,3-diisopropylisourea2×

Product 1

HCID 22594123tert-Butyl 2,6-dichloropyridine-4-carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,6-dichloropyridine-4-carboxylic acid (8.28 g, 43.1 mmol, Aldrich) in dry THF (30 ml) was added N,N′-diisopropyl-O-t-butylisourea (17 ml, 3.6 M) dropwise over 1 minute. The resulting mixture was stirred at room temperature overnight. The material was then heated to 65° C. and additional N,N′-diisopropyl-O-t-butylisourea (10 ml) was added dropwise. The mixture was stirred for 1 hour and cooled to room temperature. After removing volatiles, the remainder was purified by flash silica gel column (EtOAc/hexanes 5:95 followed by 7.5:92.5) affording tert-butyl-2,6dichloro-4-pyridine carboxylate (7.83 g, 73%) as a white solid. MS (ES+): 248.

Workup

  1. temperatureThe material was then heated to 65° C.
  2. stirringThe mixture was stirred for 1 hour
  3. temperaturecooled to room temperature
  4. customAfter removing volatiles
  5. customthe remainder was purified by flash silica gel column (EtOAc/hexanes 5:95 followed by 7.5:92.5)

Sources & evidence

ORD record
ord-1b5bdcd41910483ab6ac6556aed8746f
Source dataset
uspto-grants-2007_01
Patent number
US07157580B2

Reaction notes

Loading…