trans-Crotonyl chloride → Locostatin

HRID 133162

Reaktionsgleichung

Reaktionsgleichung von HRID 133162
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[C:19](Cl)(=[O:23])/[CH:20]=[CH:21]/[CH3:22]>C1COCC1.CCOCC>[C:19]([N:9]1[C@@H:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:12][O:11][C:10]1=[O:13])(=[O:23])/[CH:20]=[CH:21]/[CH3:22]

Komponenten

6

Edukt 3

HCID 643131trans-Crotonyl chlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 178418339Butyllithium

Produkt 1

HCID 5702600LocostatinAusbeute 109,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A solution of (4S)-4-benzyl-2-oxazolidinone (1.0 g, 5.6 mmol) in anhydrous THF (20 ml) was cooled to −78° C. n-BuLi (1.6 M solution in hexanes, 3.5 ml, 5.6 mmol) was added dropwise to the cooled solution. After 30 minutes, crotonyl chloride (0.59 ml, 6.2 mmol) was added to the mixture. The reaction was stirred for 30 minutes at −78° C., then warmed slowly to room temperature. The reaction mixture was quenched by addition of 4 ml saturated aqueous ammonium chloride. The resultant reaction mixture was diluted with ether, and washed with water and brine. The organic layer was dried using anhydrous Na2SO4 and evaporated under reduced pressure. Flash chromatography on a silica gel column using ethyl acetate/hexane (1/3) as eluent provided compound 1, i.e., (4S)-3-((E)-2-butenoyl)-4-benzyl-2-oxazolidinone, (1.50 g, 87%) as a white solid. m.p.: 83° C. IR (KBr): 3027, 2922, 2539, 1772, 1682, 1351, 1209 cm−1. 1H NMR (400 MHz, CDCl3): 7.36-7.15 (m, 7H, aromatic H's, CH═CH); 4.75-4.70 (m, 1H, CHN); 4.23-4.15 (m, 2H, CH2O); 3.33 (dd, 1H, J=3.3, 13.4 Hz, CHHPh); 2.79 (dd, 1H, J=9.5, 13.4 Hz, CHHPh); 1.98 (dd, 3H, J=1.0, 6.2 Hz, CH3). 13C NMR (100 MHz, CDCl3): δ 164.69, 153.51, 146.95, 135.28, 129.37, 128.86, 127.23, 121.74, 66.01, 55.20, 37.79, 18.50.

Aufarbeitung

  1. additionwas added dropwise to the cooled solution
  2. temperaturewarmed slowly to room temperature
  3. customThe reaction mixture was quenched by addition of 4 ml saturated aqueous ammonium chloride
  4. customThe resultant reaction mixture
  5. washwashed with water and brine
  6. customThe organic layer was dried
  7. customevaporated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-beab3f4b89724e0ab8c4a610b651d35b
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07390826B2

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