Methanol → Methyl 3-amino-3-(3,4-dimethoxyphenyl)propanoate

HRID 1258787Notes

Reaction equation

HRID 1258787 reaction equation
O=S(Cl)Cl.[NH2:5][CH:6]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)[CH2:7][C:8]([OH:10])=[O:9].[CH3:21]O>>[NH2:5][CH:6]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)[CH2:7][C:8]([O:10][CH3:21])=[O:9]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 5971823-Amino-3-(3,4-dimethoxyphenyl)propanoic acid

Product 1

HCID 11042814Methyl 3-amino-3-(3,4-dimethoxyphenyl)propanoate

Procedure

To a 50 mL round bottom flask equipped with an electromagnetic stirrer and a drying tube, 15 mL of anhydrous methanol was added. The solution was cooled on an ice-sodium chloride bath to minus 10° C., and 2 mL of SOCl2 was added slowly. The reaction mixture was allowed to react for an hour at room temperature. Then 2.25 g of 3-amino-3-(3,4-dimethoxy-phenyl)-propionic acid (prepared according to a method disclosed in J. Med. Chem. 1996, 39, 3238) was added. The reaction mixture was allowed to react for 3 hours at room temperature, and then refluxed for 40 minutes. After the solution was evaporated to remove the solvent, 100 mL of CHCl3 and saturated NaHCO3 were added, and the layers were separated. The organic layer was washed successively with 30 mL of water and saturated brine, dried over anhydrous MgSO4, filtered, evaporated, and purified by column chromatography to give 1.9 g of oil-like products. 1H NMR (CDCl3): δ 6.77-6.88 (m, 3H), 4.34 (t, 1H, J=5 Hz), 3.85 (s, 3H), 3.82 (s, 3H), 3.64 (s, 3H), 2.61 (d, 2H, J=5 Hz), 1.83 (t, 2H, J=6 Hz)

Workup

  1. customTo a 50 mL round bottom flask equipped with an electromagnetic stirrer and a drying tube
  2. additionwas added slowly
  3. customto react for an hour at room temperature
  4. addition1996, 39, 3238) was added
  5. customto react for 3 hours at room temperature
  6. temperaturerefluxed for 40 minutes
  7. customAfter the solution was evaporated
  8. customto remove the solvent, 100 mL of CHCl3 and saturated NaHCO3
  9. additionwere added
  10. customthe layers were separated
  11. washThe organic layer was washed successively with 30 mL of water and saturated brine
  12. dry with materialdried over anhydrous MgSO4
  13. filtrationfiltered
  14. customevaporated
  15. custompurified by column chromatography

Sources & evidence

ORD record
ord-046ac6c02c274fb68a873855777f8df0
Source dataset
uspto-grants-2013_06
Patent number
US08466191B2

Reaction notes

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