Chlorotrimethylsilane → 3-(3,5-Difluorophenyl)-2-((E)-hept-2-enoylamino)-propionic Acid

HRID 751756Notes

Reaction equation

HRID 751756 reaction equation
Cl[Si](C)(C)C.[F:6][C:7]1[CH:8]=[C:9]([CH:16]=[C:17]([F:19])[CH:18]=1)[CH2:10][CH:11]([C:13]([OH:15])=[O:14])[NH2:12].C(N(C(C)C)C(C)C)C.[C:29](Cl)(=[O:36])/[CH:30]=[CH:31]/[CH2:32][CH2:33][CH2:34][CH3:35]>ClCCl>[F:6][C:7]1[CH:8]=[C:9]([CH2:10][CH:11]([NH:12][C:29](=[O:36])/[CH:30]=[CH:31]/[CH2:32][CH2:33][CH2:34][CH3:35])[C:13]([OH:15])=[O:14])[CH:16]=[C:17]([F:19])[CH:18]=1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 81531DiisopropylethylamineHCID 27370453,5-DifluorophenylalanineHCID 5706481(E)-hept-2-enoyl chloride

Product 1

HCID 597533033-(3,5-Difluorophenyl)-2-((E)-hept-2-enoylamino)-propionic Acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

6.3 ml (49.7 mmol) of chlorotrimethylsilane are added to a solution of 5.0 g (24.9 mmol) of 3,5-difluoro-DL-phenylalanine in dichloromethane (150 ml) and the reaction mixture is heated to reflux for 1 h. After cooling to 0° C., 9.7 ml (55.9 mmol) of ethyldiisopropylamine are added slowly and then, dropwise, 3.64 g (24.9 mmol) of trans-2-heptenoyl chloride. The reaction mixture is stirred overnight with slow warming to RT and remains standing at RT for 2 days. For working up, it is evaporated to dryness in vacuo, the residue is taken up using diethyl ether and extracted with 2.5 pc. aqueous sodium hydrogencarbonate solution (250 ml). The aqueous phase is extracted twice with ether, and the combined organic phases are extracted a further three times with sodium hydrogencarbonate solution. The combined aqueous phases are brought to pH=2 using 1N aqueous hydrochloric acid and extracted three times with ethyl acetate. The combined ethyl acetate phases are dried over sodium sulfate, filtered, and the solvent is concentrated in vacuo. The residue is washed by stirring with diethyl ether and filtered. The filter residue is isolated, the filtrate is concentrated and again treated with diethyl ether. After repetition twice, a total of 6.12 g (79% of th.) of product are obtained as a colorless solid.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureto reflux for 1 h
  3. temperaturewith slow warming to RT
  4. waitremains standing at RT for 2 days
  5. customit is evaporated to dryness in vacuo
  6. extractionextracted with 2.5 pc
  7. extractionThe aqueous phase is extracted twice with ether
  8. extractionthe combined organic phases are extracted a further three times with sodium hydrogencarbonate solution
  9. extractionextracted three times with ethyl acetate
  10. dry with materialThe combined ethyl acetate phases are dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationthe solvent is concentrated in vacuo
  13. washThe residue is washed
  14. stirringby stirring with diethyl ether
  15. filtrationfiltered
  16. customThe filter residue is isolated
  17. concentrationthe filtrate is concentrated
  18. additionagain treated with diethyl ether
  19. customAfter repetition twice, a total of 6.12 g (79% of th.) of product are obtained as a colorless solid

Sources & evidence

ORD record
ord-9452a61ca37f4b36a001a8855e5fdbfb
Source dataset
uspto-grants-2008_07
Patent number
US07405201B2

Reaction notes

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