Trifluoroacetic acid → (2S,3S)-2-amino-N-(4-bromo-2-chloro-phenyl)-3-phenyl-butyramide

HRID 1433748

Reaction equation

HRID 1433748 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([Cl:9])[CH:3]=1.C(OC([NH:17][C@@H:18]([C@H:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH3:23])[C:19](O)=[O:20])=O)(C)(C)C.O(Cl)Cl.FC(F)(F)C(O)=O>N1C=CC=CC=1>[NH2:17][C@@H:18]([C@H:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH3:23])[C:19]([NH:6][C:5]1[CH:7]=[CH:8][C:2]([Br:1])=[CH:3][C:4]=1[Cl:9])=[O:20]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24646Chlorine monoxideHCID 6101694-Bromo-2-chloroanilineHCID 7021178(2S,3S)-2-((tert-Butoxycarbonyl)amino)-3-phenylbutanoic acid

Product 1

HCID 69009703(2S,3S)-2-amino-N-(4-bromo-2-chloro-phenyl)-3-phenyl-butyramideYield 55.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-20 °C

Procedure

4-Bromo-2-chloro-aniline (325 mg, 1.58 mmol) and (S,S)-2-tert-butoxycarbonylamino-3-phenyl-butyric acid (440 mg, 1.58 mmol) in pyridine (5 mL) were cooled to −30° C. Phosporus oxychloride (0.158 mL, 1.7 mmol) was added and stirred at −20° C. for 2 hours. The mixture was poured into ice water and extracted with ethyl acetate (3×). The combined organic extracts were washed with water, brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in dichloromethane (5 mL) at 0° C. and trifluoroacetic acid (3 mol) added. Stirring was continued for 2 hours at 0° C. The mixture was evaporated and the residue dissolved in ether. The ether solution was basified with saturated aqueous sodium bicarbonate and extracted with ether. The organic extracts were washed with brine, dried over sodium sulfate and evaporated to give (2S,3S)-2-amino-N-(4-bromo-2-chloro-phenyl)-3-phenyl-butyramide (325 mg, 55%).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in dichloromethane (5 mL) at 0° C.
  6. stirringStirring
  7. waitwas continued for 2 hours at 0° C
  8. customThe mixture was evaporated
  9. dissolutionthe residue dissolved in ether
  10. extractionextracted with ether
  11. washThe organic extracts were washed with brine
  12. dry with materialdried over sodium sulfate
  13. customevaporated

Sources & evidence

ORD record
ord-0c55c916f03d40cbb741710fd867c04b
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Linked notes

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