Hydrochloric Acid → 3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]-propionic acid

HRID 1696060Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1696060
[F:1][C:2]([F:20])([F:19])[C@H:3](OS(C(F)(F)F)(=O)=O)[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1.CCN(C(C)C)C(C)C.Cl.[NH2:31][C@@H:32]([CH2:36][S:37]([N:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)(=[O:39])=[O:38])[C:33]([OH:35])=[O:34]>C(Cl)Cl.CCOCC>[N:40]1([S:37]([CH2:36][C@H:32]([NH:31][C@@H:3]([C:4]2[CH:5]=[CH:6][C:7]([F:10])=[CH:8][CH:9]=2)[C:2]([F:1])([F:19])[F:20])[C:33]([OH:35])=[O:34])(=[O:39])=[O:38])[CH2:41][CH2:42][O:43][CH2:44][CH2:45]1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 672780012(R)-amino-3-(morpholin-4-sulfonyl)-propionic acidHCID 86610096trifluoromethanesulfonic acid 2,2,2-trifluoro-1(R)-(4-fluorophenyl)ethyl ester

Produkt 1

HCID 672773213-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]-propionic acidAusbeute 7,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of trifluoromethanesulfonic acid-2,2,2-trifluoro-1(R)-(4-fluorophenyl)ethyl ester (0.511 g, 88% pure, 1.38 mmol) in CH2Cl2 (5 mL) at rt was added DIPEA (Aldrich, 0.74 mL, 4.24 mmol) followed by the solid HCl salt of 2(R)-amino-3-(morpholin-4-sulfonyl)-propionic acid (0.292 g, 1.06 mmol) in small portions over 2 min. The initially homogeneous orange-brown solution became heterogeneous within minutes and was allowed to stir overnight at rt. The reaction mixture was then diluted with Et2O and quenched with 1M NaOH. The pH 14 aqueous layer was separated, washed with Et2O and acidified to pH 2 with 12M HCl. The aqueous layer was then extracted with Et2O. The combined Et2O extractions of the acidic solution were washed with brine and dried over anhydrous Na2SO4. Following concentration in vacuo, 0.034 g (7.7%) of 3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]propionic acid was obtained as a colorless film.

Aufarbeitung

  1. waitThe initially homogeneous orange-brown solution became heterogeneous within minutes
  2. customquenched with 1M NaOH
  3. customThe pH 14 aqueous layer was separated
  4. washwashed with Et2O
  5. extractionThe aqueous layer was then extracted with Et2O
  6. extractionThe combined Et2O extractions of the acidic solution
  7. washwere washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentration in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-d6eb2ff865654848bc89002eb5d115aa
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08163735B2

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