Hexamethylenetetramine → Ethyl 2-aminomethyl-6-methoxyisonicotinate

HRID 249732Notes

Reaction equation

HRID 249732 reaction equation
C1N2CN3CN(C2)C[N:2]1C3.Br[CH2:12][C:13]1[CH:14]=[C:15]([CH:21]=[C:22]([O:24][CH3:25])[N:23]=1)[C:16]([O:18][CH2:19][CH3:20])=[O:17]>C(Cl)(Cl)Cl>[NH2:2][CH2:12][C:13]1[CH:14]=[C:15]([CH:21]=[C:22]([O:24][CH3:25])[N:23]=1)[C:16]([O:18][CH2:19][CH3:20])=[O:17]

Participants

4

Reactant 2

HCID 4101Hexamethylenetetramine2×HCID 57791320Ethyl 2-bromomethyl-6-methoxyisonicotinate

Product 1

HCID 57791316Ethyl 2-aminomethyl-6-methoxyisonicotinate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

6.72 g (47.9 mmol) of hexamethylenetetramine (urotropin) were initially introduced in 250 ml of chloroform and a solution of 10.95 g (39.95 mmol) of ethyl 2-bromomethyl-6-methoxyisonicotinate (20c) in chloroform was added dropwise at 0° C. The mixture was stirred at RT for 4.5 hours and after this a further 3.36 g (24.0 mmol) of hexamethylenetetramine (urotropin) was added. After standing at RT for a further 60 hours, the solvent was distilled off under reduced pressure and the residue was dissolved in 500 ml of ethanol. 50 ml of concentrated HCl were added and the mixture was stirred at RT for two hours. After addition of a further 30 ml of concentrated HCl and stirring at RT overnight, it was freed from the solvent under reduced pressure. The residue was taken up in DCM and carefully treated with K2CO3 until evolution of gas was no longer observed. Subsequently, it was washed twice with saturated K2CO3 solution, and the organic phase was dried with MgSO4 and concentrated. The crude product thus obtained (7.60 g) was reacted further without further purification. LCMS-Rt: 0.74 min [M+H+]: 211.2

Workup

  1. waitAfter standing at RT for a further 60 hours
  2. distillationthe solvent was distilled off under reduced pressure
  3. dissolutionthe residue was dissolved in 500 ml of ethanol
  4. addition50 ml of concentrated HCl were added
  5. stirringthe mixture was stirred at RT for two hours
  6. additionAfter addition of a further 30 ml of concentrated HCl
  7. stirringstirring at RT overnight
  8. additioncarefully treated with K2CO3 until evolution of gas
  9. washSubsequently, it was washed twice with saturated K2CO3 solution
  10. dry with materialthe organic phase was dried with MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-4fa43990438b472191514ad974bcfd61
Source dataset
uspto-grants-2011_01
Patent number
US07863269B2

Reaction notes

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