2-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acid tert-butyl ester → 2-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acid

HRID 1192376Notes

Reaction equation

HRID 1192376 reaction equation
C([O:5][C:6](=[O:26])[CH:7]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=1[F:25])[CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])(C)(C)C>C1COCC1.CO.O>[Br:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][CH:7]([CH2:8][NH:9][C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[C:6]([OH:26])=[O:5])=[C:19]([F:25])[CH:20]=1

Participants

5

Reactant 1

HCID 675390002-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acid tert-butyl ester

Product 1

HCID 675398202-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acidYield 88.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acid tert-butyl ester (1.30 g, 3.01 mmol) was dissolved in THF (12 mL) and MeOH (12 mL). A solution of LiOH monohydrate (0.50 g, 12.0 mmol) in H2O (12 mL) was added. The mixture was heated at reflux overnight. After cooling, the solvents were evaporated in vacuo. The residue was dissolved in water and extracted with ether (2x). The aqueous phase was acidified with 1N HCl and extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated to give 2-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acid (1.00 g, 88%) as a white solid. 1H NMR (CD3OD, 400 MHz) δ 7.26 (m, 2H), 7.19 (m, 1H), 3.27 (m, 2H), 2.86 (m, 3H), 1.43 (s, 9H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux overnight
  3. temperatureAfter cooling
  4. customthe solvents were evaporated in vacuo
  5. dissolutionThe residue was dissolved in water
  6. extractionextracted with ether (2x)
  7. extractionextracted with EtOAc
  8. washThe combined organic layers were washed with brine
  9. customdried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-10248b792430410180270f0027e1192f
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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