Phenol → Carbamic acid, [(2-fluoro-4-phenoxyphenyl)methyl]-, 1,1-dimethylethyl ester

HRID 911252Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 911252
[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[F:16])([CH3:4])([CH3:3])[CH3:2].[C:18]1([OH:24])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.[Cu]Cl>[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:24][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:11][C:10]=1[F:16])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 996PhenolHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 53432589tert-Butyl [(4-bromo-2-fluorophenyl)methyl]carbamate

Produkt 1

HCID 66706560Carbamic acid, [(2-fluoro-4-phenoxyphenyl)methyl]-, 1,1-dimethylethyl esterAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 62652Cuprous chlorideKatalysatorHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

Mix under argon atmosphere (4-bromo-2-fluorobenzyl)-carbamic acid tert-butyl ester (2.12 g, 7.0 mmol), phenol (1.32 g, 14 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (129 mg, 0.7 mmol), and cesium carbonate (4.56 g, 14 mmol) in anhydrous NMP (15 mL). Degas the flask, fill with argon and add copper(I) chloride (346 mg, 3.5 mmol) quickly. Degas the flask then fill with argon and heat at 120° C. for 5 h. Cool to ambient temperature, dilute with EtOAc and filter. Wash the mixture sequentially with 0.5N aqueous HCl, 0.5N aqueous NaOH and brine. Separate the organic layer, dry over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1 and 3:1) to obtain the desired intermediate (1.28 g, 58%). GC-MS m/z: 260 [M−C4H9)+].

Aufarbeitung

  1. customDegas the flask
  2. customDegas the flask
  3. temperatureCool to ambient temperature
  4. additiondilute with EtOAc
  5. filtrationfilter
  6. washWash the mixture sequentially with 0.5N aqueous HCl, 0.5N aqueous NaOH and brine
  7. customSeparate the organic layer
  8. dry with materialdry over Na2SO4
  9. concentrationconcentrate in vacuo
  10. customPurify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1 and 3:1)

Quellen und Nachweise

ORD-Eintrag
ord-497ac4bede6f488f997b0335b454bf7d
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08022062B2

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