tert-Butyl bromoacetate → (R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate

HRID 70869

Reaktionsgleichung

Reaktionsgleichung von HRID 70869
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:29])[CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:29])[C@H:15]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:21][CH:22]=1)[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

4

Edukt 2

HCID 79177tert-Butyl bromoacetateHCID 59607884(S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one2×

Produkt 1

HCID 59607858(R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoateAusbeute 37 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-74 °C

Versuchsvorschrift

A stirred solution of (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one (intermediate 12: 5.01 g, 13.00 mmol) in THF (180 mL) is cooled to −73.8° C., and 1M THF solution of sodium hexamethyldisilylamide (14.30 mL, 14.30 mmol) is added during 5 minutes. After 30 minutes, a solution of tert-butyl bromoacetate (2.495 mL, 16.90 mmol) in THF (20 mL) is added dropwise during 5 minutes. The solution is stirred at −74° C. for 1 hour, and the reaction is quenched with saturated aqueous NH4Cl (100 mL), and warmed up to ambient temperature. The precipitated solid is filtered off and washed with ethyl acetate (50 mL). The organic phase is separated, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The obtained residue is suspended in MeOH (70 mL) and then filtered to collect the solid (5.9 g) as a mixture of the desired product and the starting material. The mixture is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=90:10 to 50:50) to give (R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate (2.40 g, 37%). HPLC retention time=1.74 minutes (condition B); MS=499.4 (m+); 443.4 (m-tBu+1; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.41 (s, 9 H) 2.42 (dd, J=16.67, 4.04 Hz, 1 H) 2.71 (ddd, J=16.55, 13.26, 9.60 Hz, 2 H) 2.87 (dd, J=16.93, 10.86 Hz, 1 H) 3.04 (dd, J=13.14, 6.32 Hz, 1 H) 3.32 (dd, J=13.39, 3.03 Hz, 1 H) 3.92 (t, J=8.34 Hz, 1 H) 4.07 (dd, J=8.97, 2.15 Hz, 1 H) 4.48-4.58 (m, 2 H) 7.20-7.30 (m, 3 H) 7.30-7.36 (m, 5 H) 7.42 (t, J=7.58 Hz, 2 H) 7.52 (d, J=8.1 Hz, 2 H) 7.56 (d, J=7.8 Hz, 2 H).

Aufarbeitung

  1. customthe reaction is quenched with saturated aqueous NH4Cl (100 mL)
  2. temperaturewarmed up to ambient temperature
  3. filtrationThe precipitated solid is filtered off
  4. washwashed with ethyl acetate (50 mL)
  5. customThe organic phase is separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. filtrationfiltered
  10. customto collect the solid (5.9 g)
  11. additionas a mixture of the desired product
  12. customThe mixture is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=90:10 to 50:50)

Quellen und Nachweise

ORD-Eintrag
ord-fd86f3c73c4c42889f8efb9c9a196772
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822534B2

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