Hydrochloric Acid → Methyl 2-amino-3-fluoro-2-(4-hydroxybenzyl)propanoate

HRID 66639Notes

Reaction equation

HRID 66639 reaction equation
[NH2:1][C:2]([CH2:14][F:15])([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].Cl.[CH3:17]O>>[NH2:1][C:2]([CH2:14][F:15])([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[C:3]([O:5][CH3:17])=[O:4]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 110420872-Amino-2-fluoromethyl-3-(4-hydroxyphenyl)propionic acid

Product 1

HCID 12768144Methyl 2-amino-3-fluoro-2-(4-hydroxybenzyl)propanoateYield 70%

Conditions

Temperature
90 °C

Procedure

With ice cooling, a suspension of 2-amino-2-fluoromethyl-3-(4-hydroxyphenyl)propionic acid (10.0 g) in absolute methanol (400 ml, dried over magnesium) is saturated with HCl gas. After heating at 90° C. overnight, the solvent is removed under reduced pressure, and the residue is dried for 3 hours under the vacuum of an oil pump. After dissolving in absolute methanol (400 ml) and saturating with HCl gas, the mixture is heated at 90° C. overnight again. After evaporation of the solvent, the residue is dissolved in water and a solution of sodium carbonate is added with stirring until pH~10. The suspension is extracted 3 times with ether; the combined ether extracts are filtered, washed carefully with water, dried (Na2SO4) and evaporated to give pure methyl 2-amino-2-fluoromethyl-3-(4-hydroxyphenyl)propionate (7.5 g, 70%) as white crystals, m.p. 130° C.; NMR (CD3OD): δ2.77 (2H, AB, JAB =14 Hz), 3.70 (3H, s), 4.50 (2H, ABX, JAB =9 Hz, JAX =JBX =JH--F =46 Hz), 6.87 (4H, A2B2 with additional fine splitting, JAB =9 Hz).

Workup

  1. customthe solvent is removed under reduced pressure
  2. customthe residue is dried for 3 hours under the vacuum of an oil pump
  3. dissolutionAfter dissolving in absolute methanol (400 ml)
  4. concentrationsaturating with HCl gas
  5. temperaturethe mixture is heated at 90° C. overnight again
  6. customAfter evaporation of the solvent
  7. dissolutionthe residue is dissolved in water
  8. additiona solution of sodium carbonate is added
  9. extractionThe suspension is extracted 3 times with ether
  10. filtrationthe combined ether extracts are filtered
  11. washwashed carefully with water
  12. dry with materialdried (Na2SO4)
  13. customevaporated

Sources & evidence

ORD record
ord-7375f0a026964ebe99e114f9fd0297de
Source dataset
uspto-grants-1982_08
Patent number
US04342780

Reaction notes

Loading…