Triphenylphosphine → [1-(4-Chloro-phenyl)-cyclobutyl]-[3-(4-trifluoromethylphenoxymethyl)-azepan-1-yl]-methanone

HRID 1160342Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1160342
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([N:14]3[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]([CH2:21][OH:22])[CH2:15]3)=[O:13])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:42][C:43]([F:52])([F:51])[C:44]1[CH:49]=[CH:48][C:47](O)=[CH:46][CH:45]=1.N(C(OCC)=O)=NC(OCC)=O.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:12]([N:14]3[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]([CH2:21][O:22][C:47]4[CH:48]=[CH:49][C:44]([C:43]([F:52])([F:51])[F:42])=[CH:45][CH:46]=4)[CH2:15]3)=[O:13])[CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Komponenten

8

Edukt 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 678744-(Trifluoromethyl)phenolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 21902048[1-(4-Chloro-phenyl)-cyclobutyl]-(3-hydroxymethyl-azepan-1-yl)-methanone

Produkt 1

HCID 21902106[1-(4-Chloro-phenyl)-cyclobutyl]-[3-(4-trifluoromethylphenoxymethyl)-azepan-1-yl]-methanoneAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a room temperature solution of [1-(4-Chloro-phenyl)-cyclobutyl]-(3-hydroxymethyl-azepan-1-yl)-methanone (0.3307 g, 1.15 mmol) in tetrahydrofuran (5.75 mL, 0.2M) under N2 was added triphenyl phosphine (0.9050 g, 3.45 mmol) and 4-trifluoromethylphenol (0.56 mL, 3.45 mmol). The solution was cooled to 0° C., then diethyl azodicarboxylate (0.54 mL, 3.1 mmol) was added dropwise over 10 minutes. When the reaction was complete by HPLC (2 hours), ethyl acetate and 10% aqueous NaOH was added. The organics were removed, dried with Na2SO4, concentrated, then taken up in Hexanes/ethyl acetate (70:30) and filtered to remove triphenyl phosphine oxide. The remaining yellow oil was purified by silica gel chromatography (3:1 to 2:3 Hexanes:ethyl acetate). The product was further purified by silica gel chromatography with 9:1 hexanes:ethyl acetate to obtain pure product in 26% yield (0.1301 g). Partial 1H NMR (CDCl3, 300 MHz) 7.55 (2H, t, J=8.7 Hz), 7.36-7.26 (4H, m), 6.92 (2H, dd, J=34.9, 8.7 Hz), 4.00-3.85 (2H, m), ppm. Partial 13C NMR (CDCl3, 75 MHz) 174.95, 161.66, 142.17, 132.35, 129.10, 126.95, 126.77, 114.61, 114.61, 71.50, 71.10 ppm. LRMS: 465.26.

Aufarbeitung

  1. additionwas added
  2. customThe organics were removed
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated
  5. filtrationfiltered
  6. customto remove triphenyl phosphine oxide
  7. customThe remaining yellow oil was purified by silica gel chromatography (3:1 to 2:3 Hexanes:ethyl acetate)
  8. customThe product was further purified by silica gel chromatography with 9:1 hexanes
  9. customethyl acetate to obtain pure product in 26% yield (0.1301 g)

Quellen und Nachweise

ORD-Eintrag
ord-4123cbd08b0646a2a71cdd2742fc5f51
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07816375B2

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