Hexane → (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one

HRID 70870

Reaktionsgleichung

Reaktionsgleichung von HRID 70870
[Li]CCCC.CCCCCC.[CH2:12]([C@H:19]1[CH2:23][O:22][C:21](=[O:24])[NH:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:25]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33](Cl)=[O:34])=[CH:27][CH:26]=1>C1COCC1.C(=O)=O.CO>[CH2:12]([C@H:19]1[CH2:23][O:22][C:21](=[O:24])[N:20]1[C:33](=[O:34])[CH2:32][CH2:31][C:28]1[CH:29]=[CH:30][C:25]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[CH:26][CH:27]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Komponenten

7

Edukt 4

HCID 8058HexaneHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 596075633-(Biphenyl-4-yl)propanoyl chloride2×HCID 178418339Butyllithium

Produkt 1

HCID 59607884(S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-oneAusbeute 60,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 21973728Carbon dioxide methanolLösungsmittel

Reaktionsbedingungen

Temperatur
-60.5 °C

Versuchsvorschrift

To a 1.6 M solution of n-BuLi in hexane (12.1 mL, 19.3 mmol) is added dropwise a solution of (S)-(−)-4-benzyl-2-oxazolidinone (3.26 g, 18.4 mmol) in dry THF (80 mL) at −71.6° C. under nitrogen over 10 minutes. The solution is warmed up to −60.5° C. while the addition, and allowed to stir for 1 hour in dry ice/MeOH bath. 3-(Biphenyl-4-yl)propanoyl chloride (intermediate 13: 5.46 g, 22.31 mmol) in dry THF (20 mL) is added dropwise at −72° C. over 5 minutes. The solution is warmed up to −56.5° C. while the addition. After stirring 10 minutes at the same temperature, the reaction mixture is allowed to warm to room temperature and stirring is continued for 3 hours. The reaction mixture is filtered, and the collected precipitate is washed with 20 mL (10 mL×2) of MeOH and then with 150 mL of H2O to give the desired product (4.26 g). The products in the mother liquor is extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is suspended in 80 mL of MeOH, and the suspension is filtered and washed with 20 mL of MeOH (1.79 g). The two fractions are mixed to give (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one (6.05 g, 85% in 2 steps). Retention time=1.77 minutes (condition A); MS (m+1)=387.3; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.77 (dd, J=13.39, 9.35 Hz, 1 H) 2.99-3.15 (m, 2 H) 3.20-3.43 (m, 3 H) 4.09-4.24 (m, 2 H), 4.68 (dddd, J=9.76, 6.73, 3.47, 3.28 Hz, 1 H) 7.18 (d, J=7.07 Hz, 2 H) 7.23-7.37 (m, 6 H) 7.42 (t, J=7.58 Hz, 2 H) 7.53 (d, J=8.1 Hz, 2 H), 7.57 (d, J=7.8 Hz, 2 H).

Aufarbeitung

  1. temperatureThe solution is warmed up to −56.5° C. while the addition
  2. temperatureto warm to room temperature
  3. stirringstirring
  4. waitis continued for 3 hours
  5. filtrationThe reaction mixture is filtered
  6. washthe collected precipitate is washed with 20 mL (10 mL×2) of MeOH

Quellen und Nachweise

ORD-Eintrag
ord-cd0f914c8e53463db5d3cc833a567297
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822534B2

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