Ethanol → HCID 66706588, compound

HRID 2041185Notes

Reaction equation

HRID 2041185 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13](Cl)=[N:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17](=[O:20])([O-])[O-:18].[K+].[K+].[C]=O.[CH2:25](O)[CH3:26]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2]>[CH2:25]([O:18][C:17]([C:13]1[CH:12]=[CH:11][C:10]([CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:15][N:14]=1)=[O:20])[CH3:26]

Participants

8

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 15449580Tert-butyl [(6-chloropyridin-3-yl)methyl]carbamateHCID 178418416HCID 178418416, compound

Product 1

HCID 66706588HCID 66706588, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 15826098HCID 15826098, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Dissolve 5-aminomethyl-2-chloro-pyridine (2 g, 14 mmol) and di-tert-butyl-dicarbonate (3.37 g, 15.4 mmol) in DCM (30 mL) and stir at room temperature for 2 h. Concentrate the reaction mixture and purify by chromatography on silica gel eluting with hexane/EtOAc (10:1 and 5:1) to give 5-(tert-butoxycarbonylamino-methyl)-2-chloro-pyridine as a yellow solid (3.6 g, 100%). MS (ES+) m/z: 243 (M+H)+. Dissolve 5-(tert-butoxycarbonylamino-methyl)-2-chloro-pyridine (1 g, 4.12 mmol) in a mixture of ethanol (15 mL) and DMF (5 mL), and add potassium carbonate (427 mg, 3.09 mmol), palladium(II) acetate (92 mg, 0.4 mmol) and diphenylphosphinoferrocene (240 mg, 0.44 mmol). Pressurize the mixture to 15 psi with carbon monoxide gas and heat the reaction mixture to 90° C. for 16 h. Filter the reaction mixture, concentrate the filtrate, and partition the residue between water and hexane/EtOAc (1:1). Dry the organic layer over Na2SO4, filter, and concentrate in vacuo. Purify the residue by chromatography on silica gel eluting with hexane/EtOAc (3:2) to give 5-(tert-butoxycarbonylamino-methyl)-pyridine-2-carboxylic acid ethyl ester as a brown oil (920 mg, 80%). MS (ES+) m/z: 281 (M+H)+. Dissolve 5-(tert-butoxycarbonylamino-methyl)-pyridine-2-carboxylic acid ethyl ester (920 mg, 3.28 mmol) in a mixture of water/THF (1:2, 15 mL) and add lithium hydroxide (87 mg, 3.61 mmol). Stir the mixture at ambient temperature for 4 h and concentrate to a solid. Dry the material by azeotrope distillation with toluene to give the desired intermediate as a brown solid (1g, 100%). MS (ES+) m/z: 253 (M+H)+.

Workup

  1. filtrationFilter the reaction mixture
  2. concentrationconcentrate the filtrate
  3. custompartition the residue between water and hexane/EtOAc (1:1)
  4. dry with materialDry the organic layer over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the residue by chromatography on silica gel eluting with hexane/EtOAc (3:2)

Sources & evidence

ORD record
ord-9ea0d7329f9b4578b095847ed8770a33
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

Loading…