Hydrochloric Acid → HCID 178521031, Verbindung

HRID 1988138Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1988138
[N+](CP(=O)([O:8][CH2:9][CH3:10])OCC)#[C-].C([Li])CCC.[Br:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]2[CH2:27]C(=O)[CH2:25]2)=[CH:20][CH:19]=1.Cl>CCOCC>[Br:17][C:18]1[CH:23]=[CH:22][C:21]([C@H:24]2[CH2:27][C@H:10]([CH:9]=[O:8])[CH2:25]2)=[CH:20][CH:19]=1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 2734699Diethyl (isocyanomethyl)phosphonateHCID 45896953-(4-Bromophenyl)cyclobutan-1-oneHCID 178418339Butyllithium

Produkt 1

HCID 178521031HCID 178521031, VerbindungAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of diethyl isocyanomethylphosphonate (0.86 mL, 5.3 mmol) in anhydrous ether (45 mL) at −78° C. under nitrogen was added n-butyl lithium (2.13 mL, 2.5 M in hexane) and the resulting mixture was stirred at −78° C. for 1 hr. Then, 3-(4-bromo-phenyl)-cyclobutanone (1 g, 4.4 mmol) in anhydrous ether (15 mL) was added dropwise over 30 minutes. The reaction mixture was allowed to warm to ambient temperature and stirred 16 hours. Concentrated hydrochloric acid (9.5 mL) was added dropwise and the reaction mixture was stirred at room temperature for 5 hrs. The mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated. The residue was chromatographed on silica gel eluting with 2-3% ethyl acetate in hexanes to provide 3-(4-bromo-phenyl)-trans-cyclobutanecarbaldehyde (281 mg, 27%) as the faster eluting isomer (A1) and 3-(4-bromo-phenyl)-cis-cyclobutanecarbaldehyde (508 mg, 48%) as the slower eluting isomer (A2). A1: 1H NMR (300 MHz, CDCl3) δ 2.37 (m, 2 H), 2.72 (m, 2 H), 3.16 (m, 1 H), 3.53 (p, J=6 Hz, 1 H), 7.09 (d, J=9 Hz, 2 H), 7.44 (d, J=9Hz, 2 H), 9.95 (s, 1 H),; (DCl/NH3) m/z 239 (M+H)+; A2: 1 H NMR (300 MHz, CDCl3) δ 2.35 (m, 2 H), 2.55 (m, 2 H), 3.21 (m, 1 H), 3.52 (p, J=6 Hz, 1 H), 7.07 (d, J=9 Hz, 2 H), 7.42 (d, J=9 Hz, 2 H), 9.73 (s, 1 H); (DCl/NH3) m/z 239 (M+H)+.

Aufarbeitung

  1. temperatureto warm to ambient temperature
  2. stirringstirred 16 hours
  3. stirringthe reaction mixture was stirred at room temperature for 5 hrs
  4. customThe mixture was partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was chromatographed on silica gel eluting with 2-3% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-8d40fa27ecbd4b65b4ec6b7a711a0edb
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07553964B2

Notizen zur Reaktion

Wird geladen…