Hydrochloric Acid → (R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid

HRID 1908961Notes

Reaction equation

HRID 1908961 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:18][C:19]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:20]=1[F:27])[CH2:10][C:11]([O:13]C(C)(C)C)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.Cl>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:18][C:19]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:20]=1[F:27])[CH2:10][C:11]([OH:13])=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 66660725HCID 66660725, compound

Product 1

HCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acidYield 73.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1.31 g of (R)-t-butyl 3-(t-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoate, 16 mL of methylene chloride, and 16 mL of trifluoroacetic acid were added to 100 mL flask and the resulting reaction solution was stirred for 6 hours. After completing the reaction, the reaction solution was concentrated under reduced pressure and 16 mL of methanol was added to the concentrated residue. The reaction solution was cooled to 0° C., 2.82 g of sodium hydrogen carbonate and 0.77 mL of di-t-butyl dicarbonate were added, and then stirred for 6 hours while the reaction temperature was naturally increased to room temperature. After completing the reaction, the reaction solution was concentrated under reduced pressure; then 30 mL of ethyl acetate and 30 mL of water were added; and then stirred for 10 minutes. An aqueous layer was isolated, cooled to 0° C., and then 2 N hydrochloric acid aqueous solution was dropped to adjust to pH 3-4. The aqueous layer was extracted with methylene chloride:methanol=10:1 solvent, dehydrated with magnesium sulfate, and then concentrated under reduced pressure to obtain 828 mg of a title compound.

Workup

  1. customthe resulting reaction solution
  2. customthe reaction
  3. concentrationthe reaction solution was concentrated under reduced pressure and 16 mL of methanol
  4. additionwas added to the concentrated residue
  5. addition2.82 g of sodium hydrogen carbonate and 0.77 mL of di-t-butyl dicarbonate were added
  6. stirringstirred for 6 hours while the reaction temperature
  7. temperaturewas naturally increased to room temperature
  8. customthe reaction
  9. concentrationthe reaction solution was concentrated under reduced pressure
  10. additionthen 30 mL of ethyl acetate and 30 mL of water were added
  11. stirringand then stirred for 10 minutes
  12. customAn aqueous layer was isolated
  13. temperaturecooled to 0° C.
  14. extractionThe aqueous layer was extracted with methylene chloride
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-87746a00af594dba9b7b7d2d9c2b63c3
Source dataset
uspto-grants-2013_12
Patent number
US08598347B2

Reaction notes

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