Hydrogen Peroxide → (R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acid

HRID 70868

Reaktionsgleichung

Reaktionsgleichung von HRID 70868
C([C@H]1COC(=O)N1[C:14](=[O:37])[C@H:15]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:27][CH:26]=1)[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])C1C=CC=CC=1.C1COCC1.OO.[Li+].[OH-:46]>O>[C:28]1([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:29]=[CH:30][C:25]([CH2:24][C@H:15]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:14]([OH:37])=[O:46])=[CH:26][CH:27]=1

Komponenten

6

Edukt 4

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 59607858(R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate

Produkt 1

HCID 59607655(R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acidAusbeute 93,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To a stirred solution of (R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate (1.20 g, 2.402 mmol) in a mixed solvent of THF (20 mL) and water (5 mL), a solution of aqueous H2O2 (0.960 mL, 9.61 mmol) and aqueous LiOH (4.80 ml, 4.80 mmol) is added at 0° C. during 5 minutes. After stirring for 1.5 hour, the reaction is quenched with saturated aqueous Na2SO3 (10 mL) at 0° C., and allowed to stir for 10 minutes at the same temperature. The reaction mixture is warmed up to ambient temperature while stirring for 0.5 hour. Then, saturated aqueous NaHCO3 and brine are added to the mixture. The product is extracted with ethyl acetate, washed with aqueous 1M HCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=75:25 to 0:100) to give (R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acid (765 mg, 93%). HPLC retention time=1.63 minutes (condition D); MS=338.6 (m−1); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.43 (s, 9 H) 2.41 (A of ABX, Jab=16.67 Hz, Jax=4.55 Hz, 1 H) 2.52-2.67 (B of ABX, Jab=16.75 Hz, Jbx=8.45 Hz, 1 H) 2.74-2.89 (m, 1 H) 3.06-3.22 (m, 2 H) 7.22-7.29 (m, 2 H) 7.30-7.37 (m, 1 H) 7.43 (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. customthe reaction is quenched with saturated aqueous Na2SO3 (10 mL) at 0° C.
  2. stirringto stir for 10 minutes at the same temperature
  3. stirringwhile stirring for 0.5 hour
  4. additionThen, saturated aqueous NaHCO3 and brine are added to the mixture
  5. extractionThe product is extracted with ethyl acetate
  6. washwashed with aqueous 1M HCl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=75:25 to 0:100)

Quellen und Nachweise

ORD-Eintrag
ord-4d4cda3830ff4f69a2f689432b29ae3b
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822534B2

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