Hydrochloric Acid → (R)-4-Benzyl-3-morpholinecarboxylic acid

HRID 2245410Notes

Reaction equation

HRID 2245410 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[C:14]([O:16]CC)=[O:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.[OH-].[Li+].[OH-].[Li+].Cl>C1COCC1.CCO.O>[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[C:14]([OH:16])=[O:15])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium Hydroxide2×HCID 168937Lithium hydroxide, monohydrate2×HCID 13543384(R)-Ethyl 4-benzylmorpholine-3-carboxylate

Product 1

HCID 1514260(R)-4-Benzyl-3-morpholinecarboxylic acidYield 94%

Reagents, catalysts & solvents 1

HCID 18504229Ethanol tetrahydrofuran waterSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl (3R)-4-(phenylmethyl)-3-morpholinecarboxylate (D46, 2.33 g, 9.36 mmol) was dissolved in a mixture of THF/EtOH/H2O (1:1:1 45 mL) before treating with Lithium Hydroxide monohydrate (0.432 g, 10.29 mmol) and heating at 50° C. overnight. Reaction not finished. Added more Lithium Hydroxide monohydrate (0.200 g, 4.76 mmol) and left heating for a further 24 hours. Added more Lithium Hydroxide (0.100 g, 2.38 mmol) and heated for a further 6 hours. Added more Lithium Hydroxide (0.100 g, 2.38 mmol) and heated for a further 16 hours. Cooled to R.T. Reaction neutralised using 2N HCl solution. Solvent evaporated. Residue partitioned between DCM and Water. Aqueous layer extracted with 10% MeOH/DCM ×5. Combined extracts dried (MgSO4). Filtered. Solvent evaporated under reduced pressure to afford the title compound as a white foam in a 94% yield.

Workup

  1. customReaction not
  2. waitleft
  3. temperatureheating for a further 24 hours
  4. temperatureheated for a further 6 hours
  5. temperatureheated for a further 16 hours
  6. temperatureCooled to R.T
  7. customReaction
  8. customSolvent evaporated
  9. customResidue partitioned between DCM and Water
  10. extractionAqueous layer extracted with 10% MeOH/DCM ×5
  11. dry with materialCombined extracts dried (MgSO4)
  12. filtrationFiltered
  13. customSolvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-9dd8dce42d2a44c8a245854a309c034b
Source dataset
uspto-grants-2010_03
Patent number
US07683056B2

Reaction notes

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