Sodium Hydroxide → (R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid

HRID 1896091Notes

Reaction equation

HRID 1896091 reaction equation
C([O:3][C:4](=[O:25])[CH2:5][CH:6]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=1[F:16])C.[OH-].[Na+]>CO.O>[C:21]([O:20][C:18]([NH:17][C@H:6]([CH2:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=1[F:16])[CH2:5][C:4]([OH:25])=[O:3])=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 57519278HCID 57519278, compound

Product 1

HCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acidYield 99.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
42.5 °C

Procedure

Refer to the common known method Tetrahedron Asymmetry, 2006, 17(2), 205-209. 3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1e (10 g, 27.7 mmol) and sodium hydroxide (3.32 g, 83.1 mmol) were dissolved in 150 mL of the mixture of methanol and water (v:v=1:1). The reaction mixture was stirred at 40-45° C. for 1-1.5 hours, then part of the solution was evaporated under reduced pressure. The residues were added with a little of water, then the pH was adjusted to 2-3 with 1 M hydrochloric acid in an ice-water bath. The mixture was extracted with ethyl acetate (200 mL×3), and the combined organic phase was washed with 200 mL of saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and then the residues were recrystallized from ethyl acetate/n-hexane to obtain the title compound (R)-3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyric acid 1f (9.2 g) as a white solid, which was directly used in the next step. MS m/z (ESI): 332.3 [M−1].

Workup

  1. custompart of the solution was evaporated under reduced pressure
  2. additionThe residues were added with a little of water
  3. customthe pH was adjusted to 2-3 with 1 M hydrochloric acid in an ice-water bath
  4. extractionThe mixture was extracted with ethyl acetate (200 mL×3)
  5. washthe combined organic phase was washed with 200 mL of saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customthe residues were recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-6ef805609a864fdba81ed67e7f5eb052
Source dataset
uspto-grants-2013_08
Patent number
US08518946B2

Reaction notes

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