Lithium Hydroxide → 5-Bromo-N-cyclopropylpyridine-2-carboxamide

HRID 861002

Reaction equation

HRID 861002 reaction equation
CO[C:3]([C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][N:6]=1)=[O:4].[Li+].[OH-].C(Cl)(=O)C(Cl)=O.[CH:20]1([NH2:23])[CH2:22][CH2:21]1>C1COCC1.CO.C([O-])(O)=O.[Na+]>[CH:20]1([NH:23][C:3]([C:5]2[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][N:6]=2)=[O:4])[CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 65578Oxalyl chlorideHCID 69828CyclopropylamineHCID 7016458Methyl 5-bromopyridine-2-carboxylate

Product 1

HCID 263700895-Bromo-N-cyclopropylpyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 516892Sodium BicarbonateSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 5-bromo-pyridine-2-carboxylic acid methyl ester (1.0 eq.) (see Synth. Commun., 1997, 27, 515) in THF:MeOH (2:1; 0.2M) was added aqueous LiOH (1M; 3.0 eq.). The mixture was stirred for 12 h, concentrated and dried under vacuum. The residue was diluted in CH2Cl2 (0.2M), oxalyl chloride (8.0 eq.) was added and the mixture was stirred for 3h, concentrated, dried under vacuum and diluted in CH2Cl2 (0.2M). Cyclopropylamine (10 eq.) was added and the mixture was stirred for 2 h, poured in saturated aqueous NaHCO3 and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography (CH2Cl2:EtOAc; 9:1) afforded the title compound as a yellow solid.

Workup

  1. concentrationconcentrated
  2. customdried under vacuum
  3. additionThe residue was diluted in CH2Cl2 (0.2M)
  4. concentrationconcentrated
  5. customdried under vacuum
  6. additiondiluted in CH2Cl2 (0.2M)
  7. stirringthe mixture was stirred for 2 h
  8. extractionextracted with EtOAc (2×)
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-d4ad99d17b1e4777882e4ac10ea89463
Source dataset
uspto-grants-2006_12
Patent number
US07153968B2

Linked notes

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