Citric Acid → HCID 86641589, compound

HRID 1771133Notes

Reaction equation

HRID 1771133 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:43]([O:47][CH2:48][C@H:49]1[NH:54][CH2:53][CH2:52][NH:51][C:50]1=[O:55])([CH3:46])([CH3:45])[CH3:44].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.C(OCC)(=O)C.N1C=CC=CC=1.C(N(CC)CC)C>[C:43]([O:47][CH2:48][C@@H:49]1[C:50](=[O:55])[NH:51][CH2:52][CH2:53][N:54]1[C:11](=[O:13])[CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])([CH3:46])([CH3:44])[CH3:45]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 11776TriphenylphosphineHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid2×HCID 58058025HCID 58058025, compound2×

Product 1

HCID 86641589HCID 86641589, compoundYield 5.6%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 1140TolueneSolvent3×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

10.0 g of (R)-3-t-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)butanoic acid (Chemical Formula 2) produced in the above Example 1 was dissolved in 450 mL of toluene in 2 L flask; 13.0 g of bis(2,2′-benzothiazolyl)disulfide and 10.2 g of triphenylphosphine were added; and then the resulting reaction solution was cooled to 0° C. While stirring the reaction solution, a solution prepared by dissolving 0.8 mL of triethylamine to 20 mL of toluene was added, and then stirred for 5 hours at room temperature. The reaction solution was cooled to 0° C., and then a solution prepared by dissolving 5.6 g of (R)-3-(t-butoxymethyl)piperazine-2-one (Chemical Formula 3) produced in the above Example 2 to 40 mL of toluene, and 2.4 mL of pyridine were slowly added. After 30 minutes, the temperature of the reaction solution was increased to room temperature, and then stirred for further 1 hour. pH of the reaction solution was adjusted to 2.5 using saturated citric acid aqueous solution, and then diluted with 400 mL of ethyl acetate. The reaction solution was washed with brine in twice, and an organic layer was dehydration-concentrated with magnesium sulfate. A residue was purified with column chromatography to obtain 838 mg of a title compound.

Workup

  1. customand then the resulting reaction solution
  2. customa solution prepared
  3. additionwas added
  4. stirringstirred for 5 hours at room temperature
  5. temperatureThe reaction solution was cooled to 0° C.
  6. customa solution prepared
  7. additionwere slowly added
  8. temperaturethe temperature of the reaction solution was increased to room temperature
  9. stirringstirred for further 1 hour
  10. washThe reaction solution was washed with brine in twice, and an organic layer
  11. concentrationwas dehydration-concentrated with magnesium sulfate
  12. customA residue was purified with column chromatography

Sources & evidence

ORD record
ord-5f8a44a7680d45ed8ec7b6cfb634b690
Source dataset
uspto-grants-2016_02
Patent number
US09249109B2

Reaction notes

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