Hydrochloric Acid → HCID 22842819, compound

HRID 2371843Notes

Reaction equation

HRID 2371843 reaction equation
C([N:8]([C@@H:16]([CH3:29])[C@@H:17]([F:28])[C:18]([O:20]CC1C=CC=CC=1)=[O:19])CC1C=CC=CC=1)C1C=CC=CC=1.Cl.C(=O)([O-])[O-].[Na+].[Na+].Cl[C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39]>CO.[OH-].[Pd+2].[OH-].O>[CH2:41]([O:40][C:38]([NH:8][C@@H:16]([CH3:29])[C@@H:17]([F:28])[C:18]([OH:20])=[O:19])=[O:39])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium Carbonate2×HCID 10387Benzyl chloroformateHCID 22842817HCID 22842817, compound

Product 1

HCID 22842819HCID 22842819, compoundYield 74.5%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Benzyl 3-(S)-N,N-dibenzylamino-2-(R)-fluorobutanoate (26.2 g, 66.8 mmol) in 370 mL of methanol containing 5.6 mL of concentrated hydrochloric acid is connected to a Parr hydrogenation apparatus with 2.62 g of palladium hydroxide as catalyst and hydrogenated in two lots at 50 psi. The lots are combined and filtered through a pad of celite. The celite is washed with water and methanol and the combined filtrates are concentrated in vacuo to give a yellow oil. The crude amino acid is taken up in 290 mL of water and treated with sodium carbonate (15.6 g, 140 mmol) and benzyl chloroformate (12.0 g, 70 mmol). After stirring for 4.5 hours, another 7.8 g of sodium carbonate is added and the reaction allowed to stir an additional 18 hours. The basic solution is washed with ether and then acidified with 500 mL of 1 hydrochloric acid. The resulting mixture is extracted with ether. Drying over magnesium sulfate followed by removal of the ether in vacuo affords 12.7 g of the desired N-benzyloxycarbonyl-3-(S)-amino-2-(R)-fluorobutanoic acid.

Workup

  1. filtrationfiltered through a pad of celite
  2. washThe celite is washed with water and methanol
  3. concentrationthe combined filtrates are concentrated in vacuo
  4. customto give a yellow oil
  5. stirringto stir an additional 18 hours
  6. washThe basic solution is washed with ether
  7. extractionThe resulting mixture is extracted with ether
  8. dry with materialDrying over magnesium sulfate
  9. customfollowed by removal of the ether in vacuo

Sources & evidence

ORD record
ord-4166711813684925ba09bf94aa886151
Source dataset
uspto-grants-1992_03
Patent number
US05096700

Reaction notes

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