Iodine → tert-butyl {(S)-1-benzyloxymethyl-2-[2-oxo-2-(3,4,5-trifluorophenyl)ethoxy]ethyl}carbamate

HRID 1677054

Reaktionsgleichung

Reaktionsgleichung von HRID 1677054
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[C:4]([F:10])[CH:3]=1.[Mg].II.FC1C=C([Mg]Br)C=C(F)C=1F.[C:25]([O:29][C:30]([N:32]1[C:37](=[O:38])[CH2:36][O:35][CH2:34][C@@H:33]1[CH2:39][O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26].[Cl-].[NH4+]>C1(C)C=CC=CC=1.O.O1CCCC1.C(OCC)C>[C:25]([O:29][C:30](=[O:31])[NH:32][C@@H:33]([CH2:39][O:40][CH2:41][C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[CH2:34][O:35][CH2:36][C:37](=[O:38])[C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[C:4]([F:10])[CH:3]=1)([CH3:28])([CH3:26])[CH3:27]

Komponenten

11

Edukt 6

HCID 807IodineHCID 25517Ammonium ChlorideHCID 6114091-Bromo-3,4,5-trifluorobenzene2×HCID 5462224MagnesiumHCID 67373012tert-butyl(S)-3-benzyloxymethyl-5-oxomorpholine-4-carboxylateHCID 178505944HCID 178505944, Verbindung

Produkt 1

HCID 67373700tert-butyl {(S)-1-benzyloxymethyl-2-[2-oxo-2-(3,4,5-trifluorophenyl)ethoxy]ethyl}carbamate

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-40 °C

Versuchsvorschrift

Under a nitrogen atmosphere, 1-bromo-3,4,5-trifluorobenzene (2 mL) was added to a diethyl ether (200 mL) suspension of magnesium (6.87 g) and iodine (trace amount) and the resultant was heated by heatgun until reaction started. 1-bromo-3,4,5-trifluorobenzene (31.7 mL) was further added dropwise. Once reflux has stopped, stirring was continued for 1.5 hours at room temperature. Under a nitrogen atmosphere, previously prepared 3,4,5-trifluorophenyl magnesium bromide was added dropwise at −35° C. or less into a tetrahydrofuran (800 mL) solution of (S)-3-benzyloxymethyl-5-oxomorpholine-4-carboxylic acid t-butyl ester (82.8 g) that was cooled to −40° C. Stirring was continued for 2 hours at −40° C., saturated ammonium chloride aqueous solution (200 mL) and water (300 mL) were added, and the temperature was raised to room temperature. Toluene (500 mL) was added, and the organic layer was partitioned. The organic layer was washed with brine. The aqueous layers were combined, ethyl acetate (400 mL) was added, and the organic layer was partitioned. The organic layers were combined and dried over anhydrous magnesium sulfate, and the solvent was removed under a vacuum. The residue was purified with silica gel column chromatography (heptane/ethyl acetate 9/1→8/2→3/1), and the title compound was obtained (82.6 g). The physical property values are as follows.

Aufarbeitung

  1. temperaturethe resultant was heated by heatgun until reaction
  2. temperatureOnce reflux
  3. stirringStirring
  4. waitwas continued for 2 hours at −40° C.
  5. temperaturethe temperature was raised to room temperature
  6. customthe organic layer was partitioned
  7. washThe organic layer was washed with brine
  8. additionethyl acetate (400 mL) was added
  9. customthe organic layer was partitioned
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was removed under a vacuum
  12. customThe residue was purified with silica gel column chromatography (heptane/ethyl acetate 9/1→8/2→3/1)

Quellen und Nachweise

ORD-Eintrag
ord-77ac8c4dc21549f4bb8232c3b3ec8b0e
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08008293B2

Verknüpfte Notizen

Wird geladen…