Lithium Hydroxide → Lithium 5-(tert-butoxycarbonylamino-methyl)-pyridine-2-carboxylate

HRID 911296Notes

Reaction equation

HRID 911296 reaction equation
C([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:8][N:7]=1)=[O:5])C.[OH-].[Li+:22]>O.C1COCC1>[C:17]([O:16][C:14]([NH:13][CH2:12][C:9]1[CH:10]=[CH:11][C:6]([C:4]([O-:5])=[O:3])=[N:7][CH:8]=1)=[O:15])([CH3:20])([CH3:18])[CH3:19].[Li+:22]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 66706588HCID 66706588, compound

Product 1

HCID 57656023Lithium 5-(tert-butoxycarbonylamino-methyl)-pyridine-2-carboxylateYield 118.1%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

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 25 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 (1 g, 100%). MS (ES+) m/z: 253 (M+H)+.

Workup

  1. concentrationconcentrate to a solid
  2. customDry the material
  3. distillationby azeotrope distillation with toluene

Sources & evidence

ORD record
ord-b641edefce2749ccba0218d5e7a71d6e
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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