HCID 22171013, Verbindung → HCID 58630661, Verbindung

HRID 2376206Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2376206
[C:1]1([CH3:23])[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([N:10]2[C@H:14]3[C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[CH2:21][C@H:13]3[O:12][C:11]2=[O:22])=[O:9])[CH:2]=1.C[Si](C)(C)N[Si](C)(C)C.[Na].[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[N:46]([C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)[N:45]=[C:44]([CH2:55]I)[CH:43]=2)[CH:38]=[CH:39][C:40]=1[Cl:41]>C1COCC1>[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[N:46]([C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)[N:45]=[C:44]([CH2:55][C@@H:7]([C:3]3[CH:2]=[C:1]([CH3:23])[CH:6]=[CH:5][CH:4]=3)[C:8]([N:10]3[C@H:14]4[C:15]5[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=5[CH2:21][C@H:13]4[O:12][C:11]3=[O:22])=[O:9])[CH:43]=2)[CH:38]=[CH:39][C:40]=1[Cl:41]

Komponenten

5

Edukt 3

HCID 22171013HCID 22171013, Verbindung2×HCID 45051731Sodium hexamethyidisilazaneHCID 58630654HCID 58630654, Verbindung2×

Produkt 1

HCID 58630661HCID 58630661, VerbindungAusbeute 83,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a stirred solution of (3aS,8aR)-3-(2-m-tolyl-acetyl)-3,3a,8,8a-tetrahydro-indeno[1,2-d]oxazol-2-one (product of Step F., 12 g, 0.039 mol) in THF (100 mL) was added 1.0 M sodium 1,1,1,3,3,3-hexamethyldisilazane (NaHMDS) (41 mL, 0.041 mol) in THF at −78° C. The mixture was stirred for 45 min at −78° C. then treated with 5-(3,4-dichloro-phenyl)-3-iodomethyl-1-(4-methoxy-phenyl)-1l-H-pyrazole (product of Step E., 18.4 g, 0.0405 mol) in THF (100 mL). The reaction mixture was allowed to warm to rt overnight and then was quenched with H2O (100 mL) and concentrated to half the volume. The aqueous layer was washed with EtOAc (3×75 mL). The extracted organic layer was washed with saturated NaCl, dried over Na2SO4, filtered and concentrated to an oil. The crude oil was purified by flash column chromatography (silica gel, 7:3 hexane/EtOAc) to obtain 20.7 g of the title compound (83%) as white foam. HPLC: Rt=11.38 (Method E). MS (ES+): mass calculated for C36H29Cl2N3O4, 638.55; m/z found 660.3 [M+Na]+. 1H NMR (400 MHz, CDCl3): 7.52 (d, J=7.6 Hz, 1H), 7.11-7.35 (m, 8H), 6.93-6.99 (m, 3H), 6.74-6.82 (m, 3H), 6.20 (s, 1H), 5.89 (d, J=6.8 Hz, 1H), 5.58 (q, J=6.1, 4.5 Hz, 1H), 5.11-5.15 (m, 1H), 3.8 (s, 3H), 3.72 (dd, J=10.6, 4.1 Hz, 1H), 3.33 (br, s, 2H), 3.07 (dd, J=9.8, 4.8 Hz, 1H), 2.37 (s, 3H).

Aufarbeitung

  1. temperatureto warm to rt overnight
  2. customwas quenched with H2O (100 mL)
  3. concentrationconcentrated to half the volume
  4. washThe aqueous layer was washed with EtOAc (3×75 mL)
  5. washThe extracted organic layer was washed with saturated NaCl
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to an oil
  9. customThe crude oil was purified by flash column chromatography (silica gel, 7:3 hexane/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-c561acb9347245b79a01a53485323e89
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07465808B2

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