Methanol → 4-Hydroxy-L-proline methyl ester hydrochloride

HRID 1267529Notes

Reaction equation

HRID 1267529 reaction equation
[C:1]([Cl:4])(=O)C.CO.[OH:7][C@H:8]1[CH2:12][NH:11][C@H:10]([C:13]([OH:15])=[O:14])[CH2:9]1>COC(C)(C)C>[ClH:4].[CH3:1][O:14][C:13](=[O:15])[C@@H:10]1[CH2:9][C@@H:8]([OH:7])[CH2:12][NH:11]1

Participants

5

Reactant 3

HCID 887MethanolHCID 5810L-HydroxyprolineHCID 6367Acetyl chloride

Product 1

HCID 114353194-Hydroxy-L-proline methyl ester hydrochlorideYield 94.1%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

Acetyl chloride (249 mL, 3.47 mol) was added dropwise to methanol (2090 mL) with stirring and cooling to maintain the temperature below 30° C. After complete addition, stirring was continued for a further 60 min. before addition of trans-4-hydroxy-L-proline (325 g, 2.48 mol) as a solid. The reaction mixture was heated to reflux for 24 h, cooled to 0° C., and tert-butyl methyl ether (TBME, 5220 mL) was added slowly over 30 min. The precipitated solid was collected on a filter and washed with ice-cold TMBE (2×1 L). The product was dried at 40° C. overnight in a vacuum to yield 424 g of the desired ester.

Workup

  1. temperaturecooling
  2. temperatureto maintain the temperature below 30° C
  3. additionAfter complete addition
  4. stirringstirring
  5. temperatureThe reaction mixture was heated
  6. temperatureto reflux for 24 h
  7. customThe precipitated solid was collected on
  8. filtrationa filter
  9. washwashed with ice-cold TMBE (2×1 L)
  10. customThe product was dried at 40° C. overnight in a vacuum

Sources & evidence

ORD record
ord-2e31cdfd45f04dd08e15fc7f192e22b7
Source dataset
uspto-grants-2003_04
Patent number
US06552016B1

Reaction notes

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