Tetrahydrofuran → (R)-(-)-N-Carbobenzyloxy-3-[2-fluoro-4-[5-hydroxymethyl-2-oxo-3-oxazolidinyl]phenyl]azetidine

HRID 428773Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 428773
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[C:6]([N:16]1[CH2:19][CH:18]([C:20]2[CH:36]=[CH:35][C:23]([NH:24][C:25]([O:27][CH2:28][C:29]3C=CC=CC=3)=[O:26])=[CH:22][C:21]=2[F:37])[CH2:17]1)([O:8][CH2:9][C:10]1[CH:15]=CC=CC=1)=[O:7].C1C[O:41][CH2:40]C1>CCCCCC>[C:6]([N:16]1[CH2:19][CH:18]([C:20]2[CH:36]=[CH:35][C:23]([N:24]3[CH2:29][C@H:28]([CH2:40][OH:41])[O:27][C:25]3=[O:26])=[CH:22][C:21]=2[F:37])[CH2:17]1)([O:8][CH2:9][C:10]1[CH:15]=[CH:4][CH:3]=[CH:2][CH:1]=1)=[O:7]

Komponenten

5

Edukt 3

HCID 8028Tetrahydrofuran2×HCID 22625683N-Carbobenzyloxy-3-(N-carbobenzyloxy-3-fluoroanilin-4-yl)azetidineHCID 178418339Butyllithium

Produkt 1

HCID 21967688(R)-(-)-N-Carbobenzyloxy-3-[2-fluoro-4-[5-hydroxymethyl-2-oxo-3-oxazolidinyl]phenyl]azetidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8058HexaneLösungsmittel

Versuchsvorschrift

n-Butyllithium (5.25 mL of a 1.6 M solution in hexane, 8.40 mmol) was added dropwise to a stirred solution of N-carbobenzyloxy-3-(N-carbobenzyloxy-3-fluoroanilin-4-yl)azetidine (Example 81, Step 4, 3.63 g, 8.36 mmol) at −78° under nitrogen in dry THF (30 mL), then stirred for 2 hr. A solution of R-glycidyl butyrate (1.21 g, 8.40 mmol) in dry THF (3.0 mL) was added and the cooling bath removed after 15 min. After 18 hr, the solvent was removed and the residue partitioned between ethyl acetate (150 mL) and saturated ammonium chloride solution (50 mL). The organic layer was washed with water (50 mL) and brine (50 mL), dried over magnesium sulfate, filtered and evaporated leaving an amber oil. Chromatography over silica gel (150 g, 40-60 μm) eluting with 2-5% methanol-chloroform gave the title compound as a sticky foam. FAB-HRMS: theory 401.1513 (M+1); meas 401.1521.

Aufarbeitung

  1. customthe cooling bath removed after 15 min
  2. waitAfter 18 hr
  3. customthe solvent was removed
  4. customthe residue partitioned between ethyl acetate (150 mL) and saturated ammonium chloride solution (50 mL)
  5. washThe organic layer was washed with water (50 mL) and brine (50 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customleaving an amber oil
  10. washChromatography over silica gel (150 g, 40-60 μm) eluting with 2-5% methanol-chloroform

Quellen und Nachweise

ORD-Eintrag
ord-d377bb3e5cf941adbec54b4915a8a7e5
Quelldatensatz
uspto-grants-2001_11
Patentnummer
US06313307B1

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