Nitrogen → (S)-3-Methyl-2-[[methyl-(2-pyridinylmethyl)amino]carbonyl]aminobutyric acid methyl ester

HRID 2379644Notes

Reaction equation

HRID 2379644 reaction equation
[CH3:1][NH:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.[CH3:10][O:11][C:12](=[O:27])[C@H:13]([CH:24]([CH3:26])[CH3:25])[NH:14][C:15]([O:17]C1C=CC=CC=1)=O.N#N>O1CCOCC1>[CH3:10][O:11][C:12](=[O:27])[C@@H:13]([NH:14][C:15]([N:2]([CH3:1])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)=[O:17])[CH:24]([CH3:25])[CH3:26]

Participants

5

Reactant 3

HCID 947NitrogenHCID 60952Methyl N-[hydroxy(phenoxy)methylidene]valinateHCID 88757Methyl(2-pyridylmethyl)amine

Product 1

HCID 10039258(S)-3-Methyl-2-[[methyl-(2-pyridinylmethyl)amino]carbonyl]aminobutyric acid methyl esterYield 92.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 2.68 g (22.0 mmol) of 2-(methylaminomethyl)-pyridine, from step 3a above, and 5.02g (20.0 mmol) of phenoxycarbonyl-L-valine methyl ester, from step 3b above, in 20 mL of 1,4-dioxane was purged with N2. The solution was then heated at reflux for four hours under a N2 atmosphere, then the solution was concentrated in vacuo. The resulting residue was dissolved in ethyl ether and extracted into 1N HCl. The aqueous layer was adjusted to about pH 9 with solid sodium carbonate and extracted twice with methylene chloride. The organic layers were combined and washed with 0.2M phosphate buffer at pH 7.0. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo, affording 5.17 g of the title product as a light yellow oil. NMR (CDCl3)δ0.95 (dd,3H), 2.19 (m, 1H), 3.03 (s,3H), 3.72 (s,3H), 4.42 (dd, 1H), 4.54 (s,2 H), 6.14 (bs,1H), 7.26 (m,2H), 7.70 (dt,1H), 8.56 (m, 1H) .

Workup

  1. temperatureThe solution was then heated
  2. temperatureat reflux for four hours under a N2 atmosphere
  3. concentrationthe solution was concentrated in vacuo
  4. dissolutionThe resulting residue was dissolved in ethyl ether
  5. extractionextracted into 1N HCl
  6. extractionextracted twice with methylene chloride
  7. washwashed with 0.2M phosphate buffer at pH 7.0
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3ddd1c086e844dab8e41182626cf790c
Source dataset
uspto-grants-1994_11
Patent number
US05362912

Reaction notes

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