Diisopropylamine → (3S,5R)-5-Methyl-3-((4R,5S)-methyl-2-oxo-5-phenyl-oxazolidine-3-carbonyl)-nonanoic acid tert-butyl ester

HRID 479052Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 479052
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C@@H:14]1[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:17][C:16](=[O:25])[N:15]1[C:26](=[O:35])[CH2:27][CH2:28][C@H:29]([CH3:34])[CH2:30][CH2:31][CH2:32][CH3:33].Br[CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39]>C1COCC1>[C:41]([O:40][C:38](=[O:39])[CH2:37][C@@H:27]([C:26]([N:15]1[C@H:14]([CH3:13])[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:17][C:16]1=[O:25])=[O:35])[CH2:28][C@H:29]([CH3:34])[CH2:30][CH2:31][CH2:32][CH3:33])([CH3:44])([CH3:43])[CH3:42]

Komponenten

6

Edukt 4

HCID 7912DiisopropylamineHCID 79177tert-Butyl bromoacetateHCID 57142278(4R,5S)-4-Methyl-3-((R)-4-methyl-octanoyl)-5-phenyl-oxazolidin-2-oneHCID 178418339Butyllithium

Produkt 1

HCID 57052159(3S,5R)-5-Methyl-3-((4R,5S)-methyl-2-oxo-5-phenyl-oxazolidine-3-carbonyl)-nonanoic acid tert-butyl esterAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
10 °C

Versuchsvorschrift

To a solution of diisopropylamine (1.8 mL, 12.6 mmol) in 30 mL THF at −78° C. was added n-butyllithium (1.6 M soln in hexanes, 7.6 mL, 12.1 mmol), and the mixture stirred 10 minutes at which time oxazolidinone 137 (3.2 g, 10.1 mmol) in 10 mL THF was added dropwise. The solution was stirred for 30 minutes, t-butyl bromoacetate (1.8 mL, 12.1 mmol) was added quickly dropwise at −50° C., and the mixture was allowed to warm slowly to 10° C. over 3 hours. The mixture was partitioned between Et2O and sat. NH4Cl (aq), the phases were separated, and the organic phase dried (MgSO4), and concentrated. The residue was purified by flash chromatography (16:1 to 8:1 hexanes:EtOAc) to provide 2.65 g (61%) of ester 138 as a colorless crystalline solid, mp=84-86° C. [α]D23+17.1 (c=1.00, CHCl3); 1H NMR (CDCl3): δ7.34 (m, 5H), 5.62 (d, J=7.3 Hz, 1H), 4.73 (quint, J=6.8 Hz, 1H), 4.29 (m, 1H), 2.67 (dd, J=9.8, 16.4 Hz, 1H), 2.40 (dd, J=5.1, 16.4 Hz, 1H), 1.69 (m, 1H), 1.38 (s, 9H), 1.28 (m, 7H), 1.08 (m, 1H), 0.88 (m, 9H); 13C NMR (CDCl3) δ176.45, 171.22, 152.71, 133.64, 128.86, 125.86, 80.83, 78.87, 55.33, 40.02, 38.21, 37.59, 36.31, 30.86, 29.29, 28.22, 23.14, 20.41, 14.36, 14.26. Anal. Calcd for C25H37NO5: C, 69.58; H, 8.64; N, 3.25. Found: C, 69.37; H, 8.68; N, 3.05.

Aufarbeitung

  1. additionwas added dropwise
  2. customThe mixture was partitioned between Et2O and sat. NH4Cl (aq)
  3. customthe phases were separated
  4. dry with materialthe organic phase dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (16:1 to 8:1 hexanes:EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-47d8dfb0c7ad4b6caf620ece80d72b6b
Quelldatensatz
uspto-grants-2003_11
Patentnummer
US06642398B2

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