Hydrochloric Acid → (2R,4R)-2-Aminomethyl-4-(2,4-difluoro-benzyl)-hexanoic Acid

HRID 132641Notes

Reaction equation

HRID 132641 reaction equation
COC([N:5]1[CH2:10][CH:9]([CH2:11][CH:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2[F:23])[CH2:13][CH3:14])[C:8](=[O:24])N(C)C1C(C)(C)C)=O.Cl.[O:31]1CCOCC1>>[NH2:5][CH2:10][C@@H:9]([CH2:11][C@H:12]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[F:23])[CH2:13][CH3:14])[C:8]([OH:24])=[O:31]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 692681512-tert-Butyl-5-[2-(2,4-difluoro-benzyl)-butyl]-3-methyl-4-oxo-tetrahydro-pyrimidine-1-carboxylic Acid Methyl Ester

Product 1

HCID 69270664(2R,4R)-2-Aminomethyl-4-(2,4-difluoro-benzyl)-hexanoic AcidYield 24%

Conditions

Temperature
110 °C

Procedure

A flask was charged with 0.5 g (1.2 mmol) of 2-tert-butyl-5-[2-(2,4-difluoro-benzyl)-butyl]-3-methyl-4-oxo-tetrahydro-pyrimidine-1-carboxylic acid methyl ester, 20 mL of dioxane, and 20 mL of conc. HCl solution. The mixture was stirred and heated at 110° C. for 4 days. The solvents were removed under reduced pressure. The residue was taken up in 20 mL of water and 4 drops of conc. HCl solution. The aqueous layer was washed with dichloromethane. The aqueous layer was collected and the water was removed under reduced pressure. The residue was treated with 2 mL of triethylamine, and the excess triethylamine was removed under reduced pressure. The remaining solid was purified by column chromatography (1:8:27 NH4OH, MeOH, dichloromethane eluent). The resulting white solid was washed with acetonitrile and dried under vacuum. This gave 80 mg (24% yield) of the titled compound as a white solid.

Workup

  1. customThe solvents were removed under reduced pressure
  2. washThe aqueous layer was washed with dichloromethane
  3. customThe aqueous layer was collected
  4. customthe water was removed under reduced pressure
  5. additionThe residue was treated with 2 mL of triethylamine
  6. customthe excess triethylamine was removed under reduced pressure
  7. customThe remaining solid was purified by column chromatography (1:8:27 NH4OH, MeOH, dichloromethane eluent)
  8. washThe resulting white solid was washed with acetonitrile
  9. customdried under vacuum

Sources & evidence

ORD record
ord-2f2f00c5cb724db38bf785910663c7d7
Source dataset
uspto-grants-2008_06
Patent number
US07388023B2

Reaction notes

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