Oxalyl chloride → HCID 67485648, compound

HRID 2233357Notes

Reaction equation

HRID 2233357 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]1[O:9][C:10]2[CH:16]=[C:15]([C:17]([OH:19])=O)[CH:14]=[C:13]([O:20][CH2:21][CH:22]([CH3:24])[CH3:23])[C:11]=2[CH:12]=1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([O:34][CH3:35])=[O:33])=[CH:28][N:27]=1>C(Cl)Cl>[CH3:7][C:8]1[O:9][C:10]2[CH:16]=[C:15]([C:17](=[O:19])[NH:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]([O:34][CH3:35])=[O:33])=[CH:28][N:27]=3)[CH:14]=[C:13]([O:20][CH2:21][CH:22]([CH3:24])[CH3:23])[C:11]=2[CH:12]=1

Participants

5

Reactant 3

HCID 65578Oxalyl chlorideHCID 737487Methyl 6-aminonicotinateHCID 67484766HCID 67484766, compound

Product 1

HCID 67485648HCID 67485648, compoundYield 49.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (410 mg, 282 μl, 3.225 mmol, 5 eq) was added to a solution of 2-methyl-4-isobutoxy-6-carboxybenzofuran (Method 2; 0.160 mg, 0.645 mmol) in DCM (5 ml) and the reaction mixture stirred for 4 hrs at ambient temperature. Further reagent was added, the reaction mixture stirred for 16 hrs, and then warmed to 40° C. As starting acid still remained, the solvent was removed in vacuo and the residue treated with neat oxalyl chloride. The reaction mixture was then concentrated in vacuo and dissolved in pyridine (5 ml); to the resulting solution was added methyl 2-aminopyridine-5-carboxylate (98 mg, 0.645 mmol). After stirring for 16 hrs the reddish solution was concentrated in vacuo and the resulting gum dissolved in DCM and chromatographed (20 g Bondelut, eluting with hexane containing ethyl acetate, 0-100%) to give the title compound (122 mg, 49.5% yield) as a colourless gum which slowly set solid; LC-MS 383 (M+H)+, 94.4% strength.

Workup

  1. additionFurther reagent was added
  2. stirringthe reaction mixture stirred for 16 hrs
  3. temperaturewarmed to 40° C
  4. customthe solvent was removed in vacuo
  5. additionthe residue treated with neat oxalyl chloride
  6. concentrationThe reaction mixture was then concentrated in vacuo
  7. dissolutiondissolved in pyridine (5 ml)
  8. stirringAfter stirring for 16 hrs the reddish solution
  9. concentrationwas concentrated in vacuo
  10. dissolutionthe resulting gum dissolved in DCM
  11. customchromatographed
  12. wash(20 g Bondelut, eluting with hexane containing ethyl acetate, 0-100%)

Sources & evidence

ORD record
ord-614235fab0fd4f44aacf317c32fe7c25
Source dataset
uspto-grants-2010_05
Patent number
US07709505B2

Reaction notes

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